Genetic Information
Gene & Transcript Details
| ID | Status | Details |
|---|---|---|
| NM_024675.4 | MANE Select | 4008 nt | 154–3714 |
| NM_024675.3 | RefSeq Select | 4069 nt | 201–3761 |
Variant Details
Clinical & Population Data
Population Frequency
gnomADClinVar
Open"This variant has been reported in ClinVar as Likely benign (2 clinical laboratories) and as Benign (1 clinical laboratories)."
COSMIC Somatic Evidence
Open
Functional Impact & Domains
Functional Domain
Computational Analysis
Pathogenicity Predictions
SpliceAISpliceAI Scores
Window: ±500bp| Effect Type | Score | Position |
|---|---|---|
| Acceptor Loss (AL) | 0.0 | -45 bp |
| Donor Loss (DL) | 0.0 | -106 bp |
| Acceptor Gain (AG) | 0.0 | -486 bp |
| Donor Gain (DG) | 0.0 | -1 bp |
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PVS1 (Not Applied)
According to VCEP guidelines the rule for PVS1 is: "Use PALB2 PVS1 Decision Tree". The evidence for this variant shows it is a synonymous change and not a null variant. Therefore, this criterion is not applied.
PS1 (Not Applied)
According to standard ACMG guidelines the rule for PS1 is: "Same amino acid change as a known pathogenic variant regardless of nucleotide change". The evidence for this variant shows no amino acid change. Therefore, this criterion is not applied.
PS2 (Not Applied)
According to standard ACMG guidelines the rule for PS2 is: "Confirmed de novo in a patient with the disease and no family history". Parental data are not available for this variant. Therefore, this criterion is not applied.
PS3 (Not Applied)
According to standard ACMG guidelines the rule for PS3 is: "Well-established functional studies show a deleterious effect". No functional studies have been performed for this variant. Therefore, this criterion is not applied.
PS4 (Not Applied)
According to VCEP guidelines the rule for PS4 is: "Strong case-control studies; p-value ≤ .05 AND (OR ≥ 3 or lower 95% CI ≥ 1.5)". There are no case-control data for this variant. Therefore, this criterion is not applied.
PM1 (Not Applied)
According to standard ACMG guidelines the rule for PM1 is: "Located in a mutational hot spot or well‐studied functional domain without benign variation". This synonymous variant is not in a known hotspot or functional domain. Therefore, this criterion is not applied.
PM2 (Supporting)
According to VCEP guidelines the rule for PM2 is: "Supporting – Variant absent in gnomAD or present in ≤ 1/300,000 alleles". The evidence for this variant shows it is not found in gnomAD. Therefore, this criterion is applied at Supporting strength.
PM3 (Not Applied)
According to VCEP guidelines the rule for PM3 is: "Use Fanconi Anemia PM3 tables" for recessive alleles. This variant is not part of a biallelic context or Fanconi Anemia case. Therefore, this criterion is not applied.
PM4 (Not Applied)
According to standard ACMG guidelines the rule for PM4 is: "Protein length changes due to in-frame indels or stop-loss variants". This is a synonymous substitution. Therefore, this criterion is not applied.
PM5 (Not Applied)
According to VCEP guidelines the rule for PM5 is: "Supporting – Apply to frameshifting or truncating variants upstream of p.Tyr1183". This variant is synonymous. Therefore, this criterion is not applied.
PM6 (Not Applied)
According to standard ACMG guidelines the rule for PM6 is: "Assumed de novo without confirmation of paternity and maternity". No de novo evidence is available. Therefore, this criterion is not applied.
PP1 (Not Applied)
According to VCEP guidelines the rule for PP1 is: "Segregation LOD thresholds". There are no segregation data. Therefore, this criterion is not applied.
PP2 (Not Applied)
According to standard ACMG guidelines the rule for PP2 is: "Missense variant in a gene with low rate of benign missense variation". This is a synonymous variant. Therefore, this criterion is not applied.
PP3 (Not Applied)
According to VCEP guidelines the rule for PP3 is: "Protein: do not use; RNA: at least one predictor shows impact on splicing". SpliceAI predicts no impact on splicing. Therefore, this criterion is not applied.
PP4 (Not Applied)
According to standard ACMG guidelines the rule for PP4 is: "Patient phenotype or family history highly specific for gene". No phenotype or family history data are provided. Therefore, this criterion is not applied.
PP5 (Not Applied)
According to standard ACMG guidelines the rule for PP5 is: "Reputable source reports variant as pathogenic". No reputable source reports this variant as pathogenic. Therefore, this criterion is not applied.
BA1 (Not Applied)
According to VCEP guidelines the rule for BA1 is: "Stand Alone – GnomAD allele frequency > 0.1%". The variant is absent in gnomAD. Therefore, this criterion is not applied.
BS1 (Not Applied)
According to VCEP guidelines the rule for BS1 is: "Strong – GnomAD allele frequency > 0.01%". The variant is absent in gnomAD. Therefore, this criterion is not applied.
BS2 (Not Applied)
According to VCEP guidelines the rule for BS2 is: "Use Fanconi Anemia BS2 tables". No relevant data. Therefore, this criterion is not applied.
BS3 (Not Applied)
According to VCEP guidelines the rule for BS3 is: "Well-established functional studies show no damaging effect". No functional data exist. Therefore, this criterion is not applied.
BS4 (Not Applied)
According to VCEP guidelines the rule for BS4 is: "Non-segregation in affected/unaffected". No segregation data. Therefore, this criterion is not applied.
BP1 (Not Applied)
According to VCEP guidelines the rule for BP1 is: "Applies to all missense variants". This is a synonymous variant. Therefore, this criterion is not applied.
BP2 (Not Applied)
According to standard ACMG guidelines the rule for BP2 is: "Observation in trans with a pathogenic variant for a recessive disorder". No such observations. Therefore, this criterion is not applied.
BP3 (Not Applied)
According to standard ACMG guidelines the rule for BP3 is: "In-frame deletions/insertions in repetitive region without a known function". Not applicable to a synonymous SNV. Therefore, this criterion is not applied.
BP4 (Supporting)
According to VCEP guidelines the rule for BP4 is: "RNA: At least one predictor shows no impact on splicing". SpliceAI predicts no splicing impact. Therefore, this criterion is applied at Supporting strength.
BP5 (Not Applied)
According to standard ACMG guidelines the rule for BP5 is: "Variant found in a case with an alternate molecular basis for disease". No such data. Therefore, this criterion is not applied.
BP6 (Supporting)
According to standard ACMG guidelines the rule for BP6 is: "Reputable source reports variant as benign but evidence not available". ClinVar entries report this variant as Benign/Likely benign. Therefore, this criterion is applied at Supporting strength.
BP7 (Not Applied)
According to VCEP guidelines the rule for BP7 is: "Observed lack of aberrant RNA defect for silent substitutions". No RNA assay data are available, only in silico predictions. Therefore, this criterion is not applied.