The U2AF1 NM_006758.3:c.470A>C (NP_006749.1:p.(Gln157Pro)) missense variant has previously been reported in somatic cancers (COSMIC; COSV52341120, n = 111 times), and lies in a statistically significant hotspot (cancerhotspots.org). Experimental evidence: Q157P altered splicing in K562 and 293T assays and increased ATR-inhibition-induced gamma-H2AX in HeLa cells versus wild-type controls. 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.U2AF1 encodes a small subunit of the U2 auxiliary factor, a protein complex essential for recognizing pre-mRNA splice sites and removing introns to produce mature messenger RNA. Alterations in U2AF1 are associated with myelodysplastic syndromes, acute myeloid leukemia, and chronic myelomonocytic leukemia. U2AF1 functions as an oncogene in cancer, where recurrent alterations can disrupt RNA splicing and contribute to the development and progression of myeloid malignancies.
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 strength: Q157P altered splicing in K562 and 293T assays and increased ATR-inhibition-induced gamma-H2AX in HeLa cells versus wild-type controls.
Met: p.Gln157Pro lies at Q157, reported as a statistically significant Cancer Hotspots hotspot, although the extracted hotspot row requires human confirmation.
Met at supporting strength: gnomAD v4.1 grpmax FAF is 3.085e-05, below the generic PM2 threshold of 0.0001, with zero homozygotes.
No benign criterion marked as applied in the recorded assessment.
VUS: PS3 supporting, PM1 moderate, and PM2 supporting provide one moderate plus two supporting criteria, insufficient for a generic ACMG/AMP pathogenic or benign combination.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 18 / 506,060 alleles. Recorded AF 3.55689e-05. Recorded homozygote count 0.
This variant is present in gnomAD v2.1 (AF= 2.38711e-05; MAF= 0.00239%, 6/251350 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 5.27872e-05; MAF= 0.00528%, 6/113664 alleles, homozygotes = 0); grpmax FAF= 2.294e-05.
Not available in gnomAD-Canada v1.0.
Recorded REVEL score: 0.555. Refer to the recorded PP3/BP4 rationale for interpretation.
1 Likely pathogenic. ClinVar API review status: criteria provided, single submitter.
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Gain-of-function; curated oncogenicity label: Likely Oncogenic.
This variant has previously been reported in somatic cancers (COSMIC; COSV52341120, n = 111 times).
This variant lies 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: 3 met · 9 not met · 12 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
For generic ACMG/AMP review of U2AF1 p.Gln157Pro, PM1 is supported by the reported Q157 mutational hotspot; PS1 is not met, PM5 cannot be assessed without a qualifying pathogenic same-residue comparator, and PP2/BP1 lack required gene-level evidence.
No segregation, parental-testing, de novo, or non-segregation evidence sufficient to apply PS2, PM6, PP1, or BS4 was identified for NM_006758.3:c.470A>C (U2AF1 p.Gln157Pro).
No VCEP covers U2AF1 in this case; generic ACMG/AMP 2015 definitions govern.
PS4 was not assessed because the available Q157P case frequency lacked a matched control comparison sufficient to calculate the required OR and 95% CI.
The literature packet contained no ai_classified_papers; extracted Q157P papers were reviewed for phenotype, case-control, and alternate-basis evidence.
PP5 and BP6 were restricted to exact-variant expert-panel assertions; the ClinVar record is a single-submitter Likely pathogenic assertion.
No criteria match.
PS3 is met at supporting strength for NM_006758.3:c.470A>C (p.Gln157Pro). Three variant-specific functional studies evaluated Q157P with appropriate wild-type comparators and assay readouts. In K562 cells expressing FLAG-tagged U2AF1 alongside endogenous protein, Q157P produced a distinct RNA-splicing program and altered 3-prime splice-site preference (PMID:25267526). In 293T minigene assays, Q157P reduced alternative splice-isoform expression relative to wild type (PMID:25311244). In stable HeLa cells expressing Q157P at similar levels to other mutants, ATR inhibition induced higher gamma-H2AX than in U2AF1-wild-type cells (PMID:30054334). These reproducible, biologically relevant cellular assays support an abnormal effect of the variant on U2AF1 function, but the evidence is from research models rather than a validated clinical diagnostic laboratory assay, so strong-level PS3 is not justified.
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
The queried p.Gln157Pro variant is reported by Cancer Hotspots as lying in a statistically significant U2AF1 Q157 hotspot. Q157 is also recurrently represented in U2AF1 mutation literature, including Q157P and Q157R in MDS cohorts and functional studies. No VCEP governs U2AF1 and no domain-table restriction applies. The hotspot extraction is flagged as partially parsed and should receive human confirmation, but the available generic ACMG evidence supports PM1.
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
PM2 is met at supporting strength. Under the generic rules, the all-comers gnomAD datasets are the default because no VCEP governs U2AF1. The variant is present at an extremely low frequency: gnomAD v2.1 exomes show AF 2.38711e-05 (6/251350 alleles; 0 homozygotes) with grpmax FAF=2.294e-05, and gnomAD v4.1 combined exomes and genomes show AF 3.55689e-05 (18/506060 alleles; 0 homozygotes) with grpmax FAF=3.085e-05. Both filtering allele-frequency values are below the supplied PM2 supporting threshold of 0.0001. The non-cancer subsets are concordant but are not required to replace the all-comers default in this generic interpretation.
Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium. ... PM2 (supporting): <= 0.0001 — SVI recommendation to downgrade PM2 to Supporting (ClinGen SVI 2020) (PMID:25741868)
The variant is NP_006749.1:p.(Gln157Pro) from NM_006758.3:c.470A>C. The available evidence identifies Q157P itself and the different substitution Q157R, but does not establish the same Gln-to-Pro amino-acid change caused by a different nucleotide change. Therefore PS1 is not met.
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change.
The variant is a missense substitution, p.(Gln157Pro), so the governing generic rule selects the REVEL path only; SpliceAI and BayesDel are not used for PP3. REVEL is 0.555, which is below the PP3 supporting threshold of >= 0.644 and therefore does not meet PP3.
Missense variant -> REVEL only. ... PP3 (supporting): >= 0.644 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
The available literature concerns somatic U2AF1 Q157P in MDS cohorts and cellular assays, not a patient phenotype or family history highly specific for a disease with a single genetic etiology. ClinVar lists the condition as not provided, and no disease-specific germline phenotype is documented for this variant.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
ClinVar variation 376024 contains an exact-variant Likely pathogenic submission from one clinical laboratory with criteria provided and single-submitter status, but no expert-panel classification. Under the requested rule, this is not a qualifying reputable exact-variant expert-panel assertion for PP5.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
BA1 is not met. The applicable all-comers gnomAD datasets show grpmax FAF values of 2.294e-05 in gnomAD v2.1 exomes (6/251350 total alleles; 0 homozygotes) and 3.085e-05 in gnomAD v4.1 combined exomes and genomes (18/506060 total alleles; 0 homozygotes). These FILTERING allele-frequency values are far below the generic stand-alone threshold of 0.05, and the relevant populations have more than 2000 observed alleles. The highest point-estimate subpopulation frequencies are also far below 5% and are not used in place of grpmax FAF.
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium. ... BA1 (stand-alone): >= 0.05 — ACMG/AMP 2015 stand-alone benign allele frequency (PMID:25741868)
BS1 is not met on the available population data. The applicable all-comers gnomAD v2.1 and v4.1 grpmax FAF values are 2.294e-05 and 3.085e-05, respectively, both far below the generic 0.01 default threshold. The observed frequencies do not require a maximum-credible-frequency exception analysis because they are not elevated; no ancestry-specific frequency signal approaches the threshold, and all relevant grpmax populations exceed 2000 observed alleles.
Allele frequency is greater than expected for the disorder. ... BS1 (strong): >= 0.01 — Generic SVI default; per-gene derivation preferred (Whiffin et al. 2017) (PMID:28518168)
BS3 is not met. The available variant-specific functional studies do not show no damaging effect; instead, they show altered U2AF1-dependent splicing and a differential cellular response to ATR inhibition for Q157P relative to wild-type controls. The evidence therefore contradicts the benign-functional direction required for BS3.
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
The variant is a missense substitution, p.(Gln157Pro), so the governing generic rule selects the REVEL path only; SpliceAI and BayesDel are not used for BP4. REVEL is 0.555, which is above the BP4 supporting threshold of <= 0.29 and lies in the indeterminate gray zone, so BP4 is not met.
Missense variant -> REVEL only. ... BP4 (supporting): <= 0.29 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
ClinVar variation 376024 has no exact-variant Benign or Likely benign expert-panel classification. Its only submission is Likely pathogenic from a single clinical laboratory, so it cannot trigger BP6 under the requested exact-variant expert-panel rule.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
PS2 cannot be assessed because the available evidence does not document a patient with the disease carrying this variant together with confirmed maternity, confirmed paternity, and no family history. The variant-specific literature concerns somatic U2AF1 Q157P in MDS cell lines or retrospective MDS cohorts and provides no parental testing or case-level de novo documentation for NM_006758.3:c.470A>C.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
PMID:33122737 reports U2AF1 p.Q157P in 7 of 234 patients with MDS (2.99%), but it provides no unaffected or population-control carrier counts for that cohort. gnomAD v4 reports 18/506060 alleles (AF 3.56e-05), but the available evidence does not establish matched ancestry or compatible carrier-level counts, so a valid case-control OR and 95% CI cannot be calculated. The governing PS4 threshold is OR >5.0 with a confidence interval excluding 1.0; no such verified estimate is available. The literature packet's ai_classified_papers list is empty, and the extracted Q157P papers were checked for case-control evidence without finding an eligible comparison.
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.
PM3 cannot be assessed because the available evidence does not establish that U2AF1-related disease is recessive, does not identify an affected proband carrying this variant with a pathogenic allele, and provides no parental or offspring testing to demonstrate that NM_006758.3:c.470A>C (p.Gln157Pro) is in trans with a pathogenic variant. The ClinVar submission records germline origin but supplies no phase or affected-proband details. The reviewed Q157P literature describes functional studies and an MDS cohort, but does not report parental phase, a pathogenic variant in trans, or cis configuration for this variant.
PM3: For recessive disorders, detected in trans with a pathogenic variant ... Note: This requires testing of parents (or offspring) to determine phase.
Q157R is a different missense change at the same residue and is described in functional and MDS literature, but the supplied evidence does not establish Q157R as a previously determined pathogenic variant under the generic PM5 rule. The exact comparator pathogenicity record is therefore missing.
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before.
PM6 cannot be assessed because no case-level evidence establishes that NM_006758.3:c.470A>C is assumed de novo in a disease-affected patient. The available Q157P publications are somatic functional or cohort studies and do not provide a proband pedigree, parental testing status, or de novo observation for this variant.
Assumed de novo, but without confirmation of paternity and maternity.
PP1 cannot be assessed because no family with multiple affected members carrying and transmitting NM_006758.3:c.470A>C is documented. The available literature reports Q157P in experimental systems or unrelated MDS cohorts and contains no family segregation, affected-relative count, or meiosis data for this variant.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease.
The supplied evidence documents recurrent U2AF1 missense mutations and functional effects of Q157P, but it does not provide the gene-level evidence required to establish both a low rate of benign missense variation and missense variants as a common disease mechanism. PP2 cannot be assessed from the available data.
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
BS2 cannot be assessed from the available evidence. gnomAD reports zero homozygotes for this variant in the all-comers and available non-cancer datasets, but that is not an observation of the variant in a healthy adult individual and does not establish the required inheritance model, expected penetrance, or early-age full penetrance. The ClinVar record provides no disease condition and no healthy-adult observation suitable for BS2.
BS2
BS4 cannot be assessed because no affected family members tested for NM_006758.3:c.470A>C are documented as lacking the variant. The available evidence contains no pedigree, affected-relative genotypes, phenotype adjudication, or non-segregation analysis; therefore lack of segregation cannot be distinguished from absent family data or phenocopy.
Lack of segregation in affected members of a family.
The available evidence does not establish that U2AF1 disease is caused primarily by truncating variants. Instead, the supplied literature focuses on recurrent Q157 and S34 missense mutations and functional gain-of-function context, but this is insufficient to formally exclude a truncating-predominant disease mechanism under BP1.
Missense variant in a gene for which primarily truncating variants are known to cause disease.
BP2 cannot be assessed because the available evidence does not establish a fully penetrant dominant U2AF1 disorder for this interpretation and provides no phase-resolved observation showing NM_006758.3:c.470A>C (p.Gln157Pro) in trans with a pathogenic variant or in cis with a pathogenic variant. The ClinVar submission records germline origin but supplies no phase or affected-proband details. The reviewed Q157P literature describes functional studies and an MDS cohort, but does not report cis/trans configuration with a pathogenic variant.
BP2: 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.
PMID:33122737 reports that one MDS patient had both Q157P and S34F, but the available extraction does not establish that the co-occurring alteration was an alternate molecular basis for that patient's disease rather than a somatic co-mutation. No sufficiently documented individual case demonstrates that the disease was explained by an alternate molecular basis, so BP5 cannot be adjudicated reliably.
Variant found in a case with an alternate molecular basis for disease.
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_006758.3:c.470A>C in U2AF1 is a missense substitution predicted to produce NP_006749.1:p.(Gln157Pro). 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 U2AF1, 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_006758.3:c.470A>C in U2AF1 is a missense substitution predicted to produce NP_006749.1:p.(Gln157Pro). 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 U2AF1, 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_006758.3:c.470A>C in U2AF1 is a missense substitution predicted to produce NP_006749.1:p.(Gln157Pro). 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 U2AF1, 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_006758.3:c.470A>C in U2AF1 is a missense substitution predicted to produce NP_006749.1:p.(Gln157Pro). 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 U2AF1, 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 U2AF1, mapped onto the exon structure of NM_006758.3. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| Remaining individuals2 / 24,826 | 8.1e-05 |
| European (non-Finnish)15 / 291,644 | 5.1e-05 |
| African/African American1 / 22,634 | 4.4e-05 |
| European (non-Finnish)6 / 113,664 | 5.3e-05 |
This variant is present in gnomAD v4.1 (AF= 3.55689e-05; MAF= 0.00356%, 18/506060 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 8.05607e-05; MAF= 0.00806%, 2/24826 alleles, homozygotes = 0); grpmax FAF= 3.085e-05.
This variant is present in gnomAD v2.1 (AF= 2.38711e-05; MAF= 0.00239%, 6/251350 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 5.27872e-05; MAF= 0.00528%, 6/113664 alleles, homozygotes = 0); grpmax FAF= 2.294e-05.
Not available in gnomAD-Canada v1.0.
The variant is a missense substitution, p.(Gln157Pro), so the governing generic rule selects the REVEL path only; SpliceAI and BayesDel are not used for PP3. REVEL is 0.555, which is below the PP3 supporting threshold of >= 0.644 and therefore does not meet PP3.
Missense variant -> REVEL only. ... PP3 (supporting): >= 0.644 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
The variant is a missense substitution, p.(Gln157Pro), so the governing generic rule selects the REVEL path only; SpliceAI and BayesDel are not used for BP4. REVEL is 0.555, which is above the BP4 supporting threshold of <= 0.29 and lies in the indeterminate gray zone, so BP4 is not met.
Missense variant -> REVEL only. ... BP4 (supporting): <= 0.29 — ClinGen SVI REVEL calibration (Pejaver et al. 2022, Am J Hum Genet) (PMID:36413997)
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_006758.3:c.470A>C in U2AF1 is a missense substitution predicted to produce NP_006749.1:p.(Gln157Pro). 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 U2AF1, 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 = 0.09). REVEL score = 0.555. BayesDel score = 0.441524.
5 paper records listed. 4 cited in the classification.
We generated K562 erythroleukemic cell lines that stably expressed transgenic FLAG-tagged U2AF1 protein (WT, S34F, S34Y, Q157P, or Q157R mutations) at modest levels in the presence of the endogenous protein.
Location Results, “U2AF1 mutations alter RNA splicing in blood cells,” paragraph 1; Figure 2
Context K562 erythroleukemic cell lines stably expressing FLAG-tagged WT, S34F, S34Y, Q157P, or Q157R U2AF1 alongside endogenous U2AF1; deep RNA sequencing and splice-site preference analysis.
Conversely, there was a reduction in relative expression of the alternative isoforms for both minigenes in cells expressing mutant Q157R and Q157P.
Location Results, “Specific effects of U2AF1 mutations in alternative splicing”; Discussion, final paragraph
Context Transient co-transfection of GH1 or FMR1 minigene reporters with WT or mutant U2AF1 constructs in 293T cells, followed by RT-PCR and isoform quantification.
To examine the effects of other MDS-associated U2AF1 mutations on the ATRi response, we generated HeLa cell lines that stably express the S34Y, Q157P, or Q157R mutant alleles at similar levels (Fig. 3D). In all the cell lines expressing these U2AF1 mutants, ATRi induced higher levels of γH2AX than in U2AF1WT-expressing cells (Fig. 3D).
Location Results, “U2AF1S34F and other MDS-associated spliceosome mutants sensitize cells to ATRi,” paragraph 4; Fig. 3D
Context Stable HeLa cell lines expressing U2AF1 wild type, S34Y, Q157P, or Q157R; ATR-inhibitor treatment with gamma-H2AX DNA-damage assessment.
13.7% (7 cases) had the 157th glutamate was substituted by proline (Q157P).
Location Results, “Mutant gene detection”; Results, “Clinical characteristics and prognostic significance of different U2AF1 mutation sites”; Table 1
Context Retrospective cohort of 234 patients with de novo MDS diagnosed from January 2016 to January 2020; targeted next-generation sequencing of a 22-gene panel.
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= 3.55689e-05; MAF= 0.00356%, 18/506060 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 8.05607e-05; MAF= 0.00806%, 2/24826 alleles, homozygotes = 0); grpmax FAF= 3.085e-05.
This variant is present in gnomAD v2.1 (AF= 2.38711e-05; MAF= 0.00239%, 6/251350 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 5.27872e-05; MAF= 0.00528%, 6/113664 alleles, homozygotes = 0); grpmax FAF= 2.294e-05.
Not available in gnomAD-Canada v1.0.
This variant has been reported in ClinVar as Likely pathogenic (1 clinical laboratory). (ClinVarID = 376024)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.09). REVEL score = 0.555. BayesDel score = 0.441524.
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Gain-of-function; curated oncogenicity label: Likely Oncogenic.
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52341120, n = 111 times).
This variant lies in a statistically significant hotspot.