Genetic Information
Gene & Transcript Details
| ID | Status | Details |
|---|---|---|
| NM_001904.3 | Alternative | 3720 nt | 269–2614 |
| NM_001904.4 | MANE Select | 3661 nt | 215–2560 |
Variant Details
Clinical & Population Data
Population Frequency
gnomADClinVar
Open""
COSMIC Somatic Evidence
Open
Functional Impact & Domains
Functional Domain
Computational Analysis
Pathogenicity Predictions
SpliceAISpliceAI Scores
Window: ±500bp| Effect Type | Score | Position |
|---|---|---|
| Acceptor Loss (AL) | 0.01 | 65 bp |
| Donor Loss (DL) | 0.0 | 216 bp |
| Acceptor Gain (AG) | 0.0 | 61 bp |
| Donor Gain (DG) | 0.0 | -24 bp |
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PVS1 (Not Applied)
According to standard ACMG guidelines, the rule for PVS1 is: 'Null variant in a gene where loss of function (LoF) is a known mechanism of disease'. The evidence for this variant shows: it is an intronic change at +24, not affecting canonical splice sites or generating a null allele. Therefore, this criterion is not applied at Not Applied strength because the variant does not result in a null effect.
PS1 (Not Applied)
According to standard ACMG guidelines, the rule for PS1 is: 'Same amino acid change as a previously established pathogenic variant regardless of nucleotide change'. The evidence for this variant shows: it is intronic with no amino acid change. Therefore, this criterion is not applied at Not Applied strength because there is no amino acid substitution.
PS2 (Not Applied)
According to standard ACMG guidelines, the rule for PS2 is: 'De novo (both maternity and paternity confirmed) in a patient with the disease and no family history'. The evidence for this variant shows: no parental or de novo testing data are available. Therefore, this criterion is not applied at Not Applied strength because de novo status has not been assessed.
PS3 (Not Applied)
According to standard ACMG guidelines, the rule for PS3 is: 'Well-established functional studies supportive of a damaging effect on the gene or gene product'. The evidence for this variant shows: no functional studies have been performed. Therefore, this criterion is not applied at Not Applied strength because functional data are not available.
PS4 (Not Applied)
According to standard ACMG guidelines, the rule for PS4 is: 'Prevalence in affected individuals significantly increased compared with controls'. The evidence for this variant shows: no case or case-control data have been reported. Therefore, this criterion is not applied at Not Applied strength because prevalence in affected individuals is not established.
PM1 (Not Applied)
According to standard ACMG guidelines, the rule for PM1 is: 'Located in a mutational hot spot or well-established functional domain without benign variation'. The evidence for this variant shows: it is intronic at +24, not within a known functional domain. Therefore, this criterion is not applied at Not Applied strength.
PM2 (Moderate)
According to standard ACMG guidelines, the rule for PM2 is: 'Absent from controls (or at extremely low frequency if recessive)'. The evidence for this variant shows: it is not found in gnomAD or other population databases (MAF=0%). Therefore, this criterion is applied at Moderate strength because the variant is absent from large control cohorts.
PM3 (Not Applied)
According to standard ACMG guidelines, the rule for PM3 is: 'Detected in trans with a pathogenic variant for recessive disorders'. The evidence for this variant shows: this is a dominant gene with no trans data, and no second allele identified. Therefore, this criterion is not applied at Not Applied strength.
PM4 (Not Applied)
According to standard ACMG guidelines, the rule for PM4 is: 'Protein length changes due to in-frame deletions/insertions or stop-loss variants'. The evidence for this variant shows: it is intronic with no predicted effect on protein length. Therefore, this criterion is not applied at Not Applied strength.
PM5 (Not Applied)
According to standard ACMG guidelines, the rule for PM5 is: 'Novel missense change at an amino acid residue where a different pathogenic missense change has been seen'. The evidence for this variant shows: it is intronic. Therefore, this criterion is not applied at Not Applied strength.
PM6 (Not Applied)
According to standard ACMG guidelines, the rule for PM6 is: 'Assumed de novo, but without confirmation of paternity and maternity'. The evidence for this variant shows: no de novo assessment performed. Therefore, this criterion is not applied at Not Applied strength.
PP1 (Not Applied)
According to standard ACMG guidelines, the rule for PP1 is: 'Co-segregation with disease in multiple affected family members'. The evidence for this variant shows: no segregation data are available. Therefore, this criterion is not applied at Not Applied strength.
PP2 (Not Applied)
According to standard ACMG guidelines, the rule for PP2 is: 'Missense variant in a gene with a low rate of benign missense variation and where missense variants are a common mechanism of disease'. The evidence for this variant shows: it is intronic, not a missense change. Therefore, this criterion is not applied at Not Applied strength.
PP3 (Not Applied)
According to standard ACMG guidelines, the rule for PP3 is: 'Multiple lines of computational evidence support a deleterious effect on the gene or gene product'. The evidence for this variant shows: computational tools (CADD=0.11, SpliceAI=0.01) predict no deleterious impact. Therefore, this criterion is not applied at Not Applied strength.
PP4 (Not Applied)
According to standard ACMG guidelines, the rule for PP4 is: 'Patient's phenotype or family history highly specific for a disease with a single genetic etiology'. The evidence for this variant shows: no phenotype data provided. Therefore, this criterion is not applied at Not Applied strength.
PP5 (Not Applied)
According to standard ACMG guidelines, the rule for PP5 is: 'Reputable source reports variant as pathogenic, but without accessible evidence'. The evidence for this variant shows: no reputable external pathogenic assertions. Therefore, this criterion is not applied at Not Applied strength.
BA1 (Not Applied)
According to standard ACMG guidelines, the rule for BA1 is: 'Allele frequency is too high for the disorder'. The evidence for this variant shows: MAF=0%. Therefore, this criterion is not applied at Not Applied strength.
BS1 (Not Applied)
According to standard ACMG guidelines, the rule for BS1 is: 'Allele frequency is greater than expected for the disorder'. The evidence for this variant shows: absent from controls. Therefore, this criterion is not applied at Not Applied strength.
BS2 (Not Applied)
According to standard ACMG guidelines, the rule for BS2 is: 'Observed in a healthy adult individual for a dominant disorder with full penetrance expected at an early age'. The evidence for this variant shows: no such observation documented. Therefore, this criterion is not applied at Not Applied strength.
BS3 (Not Applied)
According to standard ACMG guidelines, the rule for BS3 is: 'Well-established functional studies show no damaging effect on protein function or splicing'. The evidence for this variant shows: no functional studies performed. Therefore, this criterion is not applied at Not Applied strength.
BS4 (Not Applied)
According to standard ACMG guidelines, the rule for BS4 is: 'Lack of segregation in affected family members'. The evidence for this variant shows: no segregation analysis available. Therefore, this criterion is not applied at Not Applied strength.
BP1 (Not Applied)
According to standard ACMG guidelines, the rule for BP1 is: 'Missense variant in a gene where only LoF causes disease'. The evidence for this variant shows: it is intronic. Therefore, this criterion is not applied at Not Applied strength.
BP2 (Not Applied)
According to standard ACMG guidelines, the rule for BP2 is: 'Observed in trans with a pathogenic variant for dominant disorders or in cis with a pathogenic variant'. The evidence for this variant shows: no phasing data. Therefore, this criterion is not applied at Not Applied strength.
BP3 (Not Applied)
According to standard ACMG guidelines, the rule for BP3 is: 'In-frame deletions/insertions in a repetitive region without known function'. The evidence for this variant shows: it is a single-nucleotide intronic change. Therefore, this criterion is not applied at Not Applied strength.
BP4 (Supporting)
According to standard ACMG guidelines, the rule for BP4 is: 'Multiple lines of computational evidence suggest no impact on gene or gene product'. The evidence for this variant shows: CADD score 0.11, SpliceAI score 0.01, and other in silico tools predict benign. Therefore, this criterion is applied at Supporting strength because computational evidence indicates no functional impact.
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'. The evidence for this variant shows: no such case report exists. Therefore, this criterion is not applied at Not Applied strength.
BP6 (Not Applied)
According to standard ACMG guidelines, the rule for BP6 is: 'Reputable source reports variant as benign, but without accessible evidence'. The evidence for this variant shows: no reputable benign assertions. Therefore, this criterion is not applied at Not Applied strength.
BP7 (Not Applied)
According to standard ACMG guidelines, the rule for BP7 is: 'Synonymous variant with no predicted impact on splicing'. The evidence for this variant shows: it is intronic, not synonymous coding. Therefore, this criterion is not applied at Not Applied strength.