The G6PD NM_001360016.2:c.563C>T (NP_001346945.1:p.(Ser188Phe)) missense variant has not previously been reported in somatic cancers (COSMIC). Experimental evidence: G6PD Mediterranean activity was 0.64–1.1 IU/g Hb, with a separate infant showing 8% residual activity, but direct controlled variant-versus-wild-type assays were unavailable. Based on available guidelines, this variant is considered to be a Variant of Uncertain Significance (VUS).
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.G6PD encodes an enzyme that helps cells produce NADPH, which protects against oxidative damage and supports important biosynthetic reactions. Changes that reduce G6PD activity can cause G6PD deficiency, leading to neonatal jaundice, episodes of red blood cell breakdown, or chronic hemolytic anemia. G6PD is not known to have a primary role in cancer.
The recorded framework is Generic ACMG/AMP 2015 with ClinGen SVI recommendations. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
Met at supporting: G6PD Mediterranean activity was 0.64–1.1 IU/g Hb, with a separate infant showing 8% residual activity, but direct controlled variant-versus-wild-type assays were unavailable.
No benign criterion marked as applied in the recorded assessment.
VUS: PS3 supporting is the only applied criterion, and one supporting criterion does not satisfy a generic ACMG pathogenic or benign combination rule.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 1,705 / 1,209,752 alleles. Recorded AF 0.00140938. Recorded homozygote count 23.
This variant is present in gnomAD v2.1 (AF= 0.00230096; MAF= 0.23010%, 471/204697 alleles, homozygotes = 6) and has highest observed frequency in the South Asian population (AF= 0.0173498; MAF= 1.73498%, 331/19078 alleles, homozygotes = 4); grpmax FAF= 0.0158107.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0021542738012508686, 31/14390 alleles, homozygotes = 0).
Recorded SpliceAI maximum delta score: 0.024. Refer to the recorded PP3/BP4 rationale for interpretation.
55 Pathogenic · 6 Likely pathogenic. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
No standalone functional evidence summary is recorded in evidence_summary.functional.
This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under Generic ACMG/AMP 2015 with ClinGen SVI recommendations, with the data and sources behind each one.
28 criteria with recorded statuses: 1 met · 6 not met · 17 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
The G6PD CSPEC is listed but has no released criteria, so generic ACMG/AMP rules govern.
No criterion in this group is met from the supplied evidence: affected-cohort observations do not establish PS4 without an appropriate control comparison, the index phenotype is not supplied for PP4, no alternate molecular basis is supplied for BP5, and ClinVar has no exact-variant expert-panel classification for PP5 or BP6.
Population evidence does not support BA1 because the maximum observed ancestry frequency is 4.204%, below the supplied 5% threshold.
PM2 is not met because the variant is present in multiple control datasets at frequencies well above the supplied 0.0001 threshold.
BS1 is not assessed because the ancestry-enriched founder frequency cannot be compared with a disorder-specific maximum credible frequency without explicit prevalence, penetrance, and allelic-heterogeneity inputs.
BS2 is not assessed because population databases report aggregate genotype counts without establishing a healthy adult hemizygote.
No criteria match.
PS3 is met at supporting strength. The exact variant NM_001360016.2:c.563C>T (p.Ser188Phe), also called G6PD Mediterranean, was evaluated through quantitative erythrocyte G6PD activity assays in multiple clinical/population studies. In an Indian cohort, the G6PD Mediterranean type was specifically associated with 0.64–1.1 IU/g Hb enzyme activity (PMID:18568599). In a Swedish newborn-screening study, the exact variant was found on 16 alleles; one compound-heterozygous infant had 8% residual G6PD activity, and 14 of 16 individuals with activity <=10% of normal carried c.563C>T (PMID:33072997). A Hellenic study identified the same 188 Ser>Phe variant in 231 of 299 deficient males, with the deficient cohort showing 0.1–5% of normal activity, although no variant-specific activity value was reported (PMID:10782016). A Saudi study also identified p.Ser188Phe as the Mediterranean haplotype in a cohort assessed by quantitative spectrophotometry, but did not provide a variant-specific activity value in the extracted evidence (PMID:23006493). These are clinically relevant quantitative enzyme-function measurements and are concordant with reduced G6PD function, but the evidence lacks a direct purified-protein or engineered-cell comparison with matched wild-type and assay controls and does not establish reproducibility at the highest functional-evidence level; therefore strong PS3 is not justified.
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
PM2 is not met. The variant is present in gnomAD v4.1 at AF 0.0014093798 (1705/1209752 alleles; 23 homozygotes) and in gnomAD v2.1 at AF 0.0023009619 (471/204697 alleles; 6 homozygotes), with substantially higher ancestry-specific frequencies. These observations are far above the supplied generic PM2 supporting threshold of <=0.0001 and are incompatible with absence or extremely low frequency in controls.
Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
PP3 is evaluated on the single path matching the variant consequence. NM_001360016.2:c.563C>T is a missense variant producing p.(Ser188Phe), so REVEL is the applicable predictor and SpliceAI is excluded. No REVEL score is available for this variant; therefore the applicable computational result is indeterminate and PP3 is not met. The available BayesDel score (0.453964) is not usable because no generic ACMG-strength calibration is established, and the SpliceAI max delta of 0.024 cannot support PP3 for a missense variant.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
BA1 is not met. The highest reported gnomAD v4.1 ancestry frequency is 0.0420399724 in the Middle Eastern population (183/4353 alleles), below the supplied generic stand-alone threshold of 0.05; the all-comers frequency is 0.0014093798 (1705/1209752 alleles). The generic rule therefore is not satisfied, and the variant is an SNV rather than an indel subject to the stated calling caveat.
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
BS3 is not met. No study in the reviewed evidence demonstrates that NM_001360016.2:c.563C>T (p.Ser188Phe) has normal G6PD function or normal splicing. The available quantitative enzyme-activity observations instead report markedly reduced activity for G6PD Mediterranean or for individuals carrying the exact variant, including 0.64–1.1 IU/g Hb in one cohort and 8% residual activity in a compound-heterozygous infant. The studies do not provide a well-established benign functional result or adequate matched controls that could support BS3.
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
NM_001360016.2:c.563C>T is a missense variant producing p.Ser188Phe. BP1 applies to a gene for which primarily truncating variants are known to cause disease. PMID:33072997 states that most G6PD disease-causing variants are either missense or nonsense and gives c.563C>T (p.Ser188Phe) as a disease-associated missense example. The available evidence does not support a primarily truncating disease mechanism for G6PD, so BP1 is not met.
Missense variant in a gene for which primarily truncating variants are known to cause disease.
BP4 is evaluated on the single path matching the variant consequence. NM_001360016.2:c.563C>T is a missense variant producing p.(Ser188Phe), so REVEL is the applicable predictor and SpliceAI is excluded. No REVEL score is available for this variant; therefore the applicable computational result is indeterminate and BP4 is not met. The available BayesDel score (0.453964) is not usable because no generic ACMG-strength calibration is established, and the SpliceAI max delta of 0.024 cannot support BP4 for a missense variant despite being below the splice-path cutoff.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
The variant is G6PD p.Ser188Phe (c.563C>T), and the reviewed studies establish this exact pathogenic disease-associated variant. However, no reviewed source documents a distinct nucleotide substitution that produces the same p.Ser188Phe amino-acid change. Because PS1 requires the same amino-acid change from a previously established pathogenic variant regardless of nucleotide change, the available evidence is insufficient to apply PS1.
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change.
No case-level evidence documents a proband with the disease, absence of family history, or confirmed maternity and paternity for a de novo occurrence of NM_001360016.2:c.563C>T. Without both parental confirmations and the required clinical context, PS2 cannot be assessed.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
The governing rule requires a significantly increased prevalence in affected individuals compared with controls and, under its stated note, an odds ratio or relative risk >5.0 with a confidence interval excluding 1.0. The reviewed exact-variant papers report affected cohorts but do not provide an unaffected or population-control comparison for c.563C>T/p.Ser188Phe: Dallol et al. report 29/164 haplotypes (17.79%) in a Saudi suspected-deficiency cohort; the Swedish newborn-screening study reports 16 alleles in 10,098 screened infants and 14/16 among infants with activity <=10% of normal; and Rinaldi et al. report 231/299 deficient Hellenic males. These are not sufficient to calculate the required case-control OR/RR and 95% CI. The literature_pass.json PS4 index entries (PMID:22876374 and PMID:35753512) have no corresponding paper_extracts entries or ai_classified_papers verification, so they cannot establish PS4. No numeric inequality can be evaluated because no case-control effect estimate and confidence interval are available.
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. ... Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0.
The variant is G6PD p.Ser188Phe. The governing G6PD CSPEC record has no released criterion specifications, and vcep_materials.json reports an empty domain_tables object, so there is no authoritative approved G6PD critical-domain entry to assess at residue 188. The Cancer Hotspots result for G6PD S188 is negative, and no reviewed evidence establishes residue 188 as a mutational hotspot or critical, well-established functional domain without benign variation. The generic PM1 requirement therefore cannot be assessed from the available evidence.
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
The Swedish newborn-screening study reports one patient compound heterozygous for c.[267+5G>A];[563C>T] with 8% residual G6PD activity, which establishes an allelic pairing but does not establish that c.267+5G>A is pathogenic; it is described only as an intronic variant possibly causing aberrant splicing and not described before. The available report therefore does not provide a confirmed pathogenic variant in trans, so PM3 cannot be applied. Parent or offspring testing is not reported as an independent phase confirmation.
For recessive disorders, detected in trans with a pathogenic variant ... Note: This requires testing of parents (or offspring) to determine phase.
The variant changes G6PD Ser188 to Phe. The PM5 candidate collection contains zero total candidates and zero same-residue candidates, and the reviewed papers report p.Ser188Phe itself rather than a different missense substitution at residue 188. No different missense change at residue 188 has therefore been established as pathogenic in the available evidence.
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before.
No case-level evidence documents an assumed de novo occurrence of NM_001360016.2:c.563C>T. The available information does not establish a proband with the disease or indicate whether maternity or paternity was unconfirmed, so PM6 cannot be assessed.
Assumed de novo, but without confirmation of paternity and maternity.
No family-level evidence documents multiple affected relatives carrying NM_001360016.2:c.563C>T, the number of informative meioses, or phenotype-consistent cosegregation. PP1 therefore cannot be assessed.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease.
The reviewed G6PD literature supports a missense disease mechanism, but it does not provide a validated gene-level rate or threshold showing low benign missense variation. Because PP2 requires both low benign missense variation and missense variants as a common disease mechanism, the available evidence is insufficient to apply PP2.
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
The governing rule requires a patient's phenotype or family history that is highly specific for a disease with a single genetic etiology. The case evidence supplied for this variant does not provide an index-patient phenotype or family history sufficiently specific for G6PD deficiency, and the reviewed literature reports cohort-level deficiency ascertainment rather than a documented phenotype for this case. Therefore PP4 cannot be assessed.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
The governing rule concerns a reputable recent pathogenic report whose underlying evidence is unavailable for independent evaluation. Under the specified generic rule for this interpretation, PP5 may be applied only for an exact-variant ClinVar expert-panel classification. ClinVar reports this variant as Pathogenic/Likely pathogenic with no expert-panel submission, and the available submissions are ordinary laboratory or aggregate assertions. Therefore PP5 is not triggered; an expert-panel classification is the missing requirement.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
BS1 is not assessed. gnomAD v4.1 shows an overall AF of 0.0014093798 and a Middle Eastern AF of 0.0420399724 (183/4353 alleles; 4 homozygotes), while gnomAD v2.1 shows a South Asian AF of 0.0173498270 (331/19078 alleles; 4 homozygotes). The ancestry-enriched frequency is consistent with the reported Mediterranean founder context, but the generic BS1 question is whether the frequency is greater than expected for this disorder. The supplied 1% value is only a default, and no maximum-credible-frequency calculation with explicit prevalence, penetrance, and allelic-heterogeneity inputs is available; applying the default alone would be inappropriate for this X-linked, ancestry-enriched G6PD variant.
Allele frequency is greater than expected for the disorder.
BS2 is not assessed. gnomAD v4.1 reports 23 homozygotes overall, including 4 in the Middle Eastern population and 14 in the South Asian population; gnomAD v2.1 reports 6 homozygotes overall. These aggregate counts do not identify healthy adults, and the X-linked rule requires an observed healthy adult hemizygote. The available population records provide no individual phenotype, age, or clinical follow-up establishing that requirement.
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
No family-level evidence identifies affected family members who lack NM_001360016.2:c.563C>T or establishes that the variant fails to segregate with disease. BS4 cannot be assessed without affected relatives, their phenotypes, and their variant results.
Lack of segregation in affected members of a family.
No observation of c.563C>T in cis with a pathogenic variant is documented. The available compound-heterozygous observation is not evidence for the BP2 dominant-disorder branch because G6PD deficiency is being evaluated as a recessive/X-linked disorder, and it does not establish cis phase. Therefore the BP2 evidence requirement is not assessable from the available data.
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
The governing rule requires the variant to be found in a case with an alternate molecular basis for disease. The supplied case evidence does not document an alternate pathogenic molecular diagnosis in the case, and none of the reviewed variant papers establishes such an alternate molecular basis for this patient. BP5 therefore cannot be assessed.
Variant found in a case with an alternate molecular basis for disease.
The governing rule concerns a reputable recent benign report whose underlying evidence is unavailable for independent evaluation. Under the specified generic rule for this interpretation, BP6 may be applied only for an exact-variant ClinVar expert-panel classification of Benign or Likely benign. ClinVar has no expert-panel submission for this variant and reports Pathogenic/Likely pathogenic aggregate classifications, not an expert-panel benign classification. Therefore BP6 is not triggered; an exact-variant expert-panel benign classification is the missing requirement.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
PVS1 (ClinGen SVI PVS1 recommendations, PMC6185798, pvs1_generic_framework) applies only to null variant classes — nonsense, frameshift, canonical ±1/2 splice-consensus, translation-initiation-codon loss, and stop-loss variants — each expected to trigger nonsense-mediated decay or otherwise abolish normal protein function. NM_001360016.2:c.563C>T in G6PD is a missense substitution predicted to produce NP_001346945.1:p.(Ser188Phe). As a result, no null-variant mechanism (nonsense-mediated decay, truncation, or canonical splice disruption) is triggered by this variant class, so PVS1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PVS1 for G6PD, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_null_variant_class
PM4 (Richards et al. 2015, PMID:25741868) applies to protein length changes: in-frame insertions/deletions in a non-repetitive region, or stop-loss variants that extend the protein past the reference stop codon. NM_001360016.2:c.563C>T in G6PD is a missense substitution predicted to produce NP_001346945.1:p.(Ser188Phe). As a result, no change in protein length occurs, so there is nothing for this criterion to evaluate, so PM4's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM4 for G6PD, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_stop_loss_or_nonrepeat_indel
BP3 (Richards et al. 2015, PMID:25741868) applies to in-frame insertions/deletions located in a repetitive region without a known function. NM_001360016.2:c.563C>T in G6PD is a missense substitution predicted to produce NP_001346945.1:p.(Ser188Phe). As a result, the variant does not alter protein length within a repeat region, so there is nothing for this criterion to evaluate, so BP3's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP3 for G6PD, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_repeat_region_indel
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_001360016.2:c.563C>T in G6PD is a missense substitution predicted to produce NP_001346945.1:p.(Ser188Phe). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for G6PD, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
Every interpreted variant in G6PD, mapped onto the exon structure of NM_001360016.2. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| Middle Eastern183 / 4,353 | 0.0424 hom |
| South Asian1061 / 56,814 | 0.01914 hom |
| Ashkenazi Jewish122 / 22,030 | 0.00551 hom |
| Remaining individuals156 / 47,600 | 0.00333 hom |
| African/African American12 / 57,216 | 0.00021 |
| European (non-Finnish)170 / 894,832 | 0.000191 hom |
| Admixed American1 / 45,850 | 2.2e-05 |
| South Asian331 / 19,078 | 0.0174 hom |
| Ashkenazi Jewish45 / 7,653 | 0.0059 |
| Remaining individuals26 / 5,322 | 0.00491 hom |
| European (non-Finnish)65 / 92,279 | 0.00071 hom |
| African/African American4 / 18,967 | 0.00021 |
This variant is present in gnomAD v4.1 (AF= 0.00140938; MAF= 0.14094%, 1705/1209752 alleles, homozygotes = 23) and has highest observed frequency in the Middle Eastern population (AF= 0.04204; MAF= 4.20400%, 183/4353 alleles, homozygotes = 4); grpmax FAF= 0.0370614.
This variant is present in gnomAD v2.1 (AF= 0.00230096; MAF= 0.23010%, 471/204697 alleles, homozygotes = 6) and has highest observed frequency in the South Asian population (AF= 0.0173498; MAF= 1.73498%, 331/19078 alleles, homozygotes = 4); grpmax FAF= 0.0158107.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0021542738012508686, 31/14390 alleles, homozygotes = 0).
PP3 is evaluated on the single path matching the variant consequence. NM_001360016.2:c.563C>T is a missense variant producing p.(Ser188Phe), so REVEL is the applicable predictor and SpliceAI is excluded. No REVEL score is available for this variant; therefore the applicable computational result is indeterminate and PP3 is not met. The available BayesDel score (0.453964) is not usable because no generic ACMG-strength calibration is established, and the SpliceAI max delta of 0.024 cannot support PP3 for a missense variant.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
BP4 is evaluated on the single path matching the variant consequence. NM_001360016.2:c.563C>T is a missense variant producing p.(Ser188Phe), so REVEL is the applicable predictor and SpliceAI is excluded. No REVEL score is available for this variant; therefore the applicable computational result is indeterminate and BP4 is not met. The available BayesDel score (0.453964) is not usable because no generic ACMG-strength calibration is established, and the SpliceAI max delta of 0.024 cannot support BP4 for a missense variant despite being below the splice-path cutoff.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_001360016.2:c.563C>T in G6PD is a missense substitution predicted to produce NP_001346945.1:p.(Ser188Phe). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for G6PD, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). BayesDel score = 0.453964.
10 paper records listed. 4 cited in the classification.
By means of MboII endonuclease digestion, 231 out of 299 individuals were found to be hemizygotes for the G6PD Mediterranean variant (188 Ser→Phe).
Location Results, paragraphs 1–2; Table 1 and Table 2
Context Hellenic cohort of 299 G6PD-deficient male subjects; MboII endonuclease digestion was used to identify the G6PD Mediterranean variant.
"the G6PD Mediterranean variant (188 Ser ! Phe) predominates throughout the Mediterranean and Middle East"; "The enzyme activity of the G6PD Med type found in these populations was within the range of 0.64–1.1 IU/g Hb"
Location Introduction, paragraph 3; Results and discussion, paragraph 2
Context A total of 3480 males from 14 tribal communities were screened by fluorescent spot testing and quantitative enzyme assay; deficient samples were molecularly characterized by PCR-RFLP.
Mediterranean, characterised by a single p.Ser188Phe mutation (29/164, 17.79%)
Location Results, 6-locus haplotyping paragraph
Context Saudi cohort of 249 individuals with suspected G6PD deficiency; six-locus haplotyping was based on DNA sequencing, with quantitative G6PD enzyme activity measured by UV/kinetic spectrophotometry.
Most disease-causing variants are either missense or nonsense, the latter only found in heterozygous females since the complete loss of enzyme activity is considered not to be compatible with life [2]. Disease-causing variants have often been named after the geographic area where they are common, for example the “Mediterranean” variant, c.563C>T (p.(Ser188Phe)) [17].
Location Section 1.2, The G6PD Gene
Context Swedish newborn-screening study of 10,098 dried blood spot samples; G6PD activity was measured by a fluorometric assay, and low-activity samples underwent Sanger sequencing of G6PD exons 2–13 and exon/intron boundaries.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
This variant is present in gnomAD v4.1 (AF= 0.00140938; MAF= 0.14094%, 1705/1209752 alleles, homozygotes = 23) and has highest observed frequency in the Middle Eastern population (AF= 0.04204; MAF= 4.20400%, 183/4353 alleles, homozygotes = 4); grpmax FAF= 0.0370614.
This variant is present in gnomAD v2.1 (AF= 0.00230096; MAF= 0.23010%, 471/204697 alleles, homozygotes = 6) and has highest observed frequency in the South Asian population (AF= 0.0173498; MAF= 1.73498%, 331/19078 alleles, homozygotes = 4); grpmax FAF= 0.0158107.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0021542738012508686, 31/14390 alleles, homozygotes = 0).
This variant has been reported in ClinVar as Pathogenic (55 clinical laboratories) and as Likely pathogenic (6 clinical laboratories). (ClinVarID = 100057)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). BayesDel score = 0.453964.
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.