Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with ClinVar but not with the Allele Registry data
  • No CSPEC related information was provided by the message!
  • No Criteria Specification was provided in the publication event for the variant classifaction.
  • The Criteria Specification shown below is a best-estimate based on the VCEP, gene, disease, and publication date.

Variant: NM_000038.6:c.509_512del

804 (ClinVar)

Gene: APC
Condition: familial adenomatous polyposis 1 (MONDO:0021056)
Inheritance Mode: Autosomal dominant inheritance
UUID: 80cd255c-1080-43ea-9aa9-61e2d39fd0c4
Approved on: 2023-02-18
Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.509_512del
NM_000038.6(APC):c.509_512del (p.Asp170fs)

Pathogenic

Met criteria codes 4
PP1_Moderate PS4 PM2_Supporting PVS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP
The c.509_512del (p.Asp170Valfs*4) variant in APC is a frameshift variant located between codon 49 and 2645 and predicted to cause a premature stop codon in exon 5 in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has been reported in > 8 probands meeting phenotypic criteria, resulting in a total phenotype score of 5 (PS4, PMID 1324223, Ambry Genetics, Invitae, Leiden, Bonn, Melbourne internal data). In addition, this variant has been reported to segregate with FAP in > 10 affected meioses in 1 family (PP1_Moderate; PMID 1324223). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: PVS1, PS4, PM2_Supporting, PP1_Moderate (VCEP specifications version 1; date of approval: 12/12/2022).
Met criteria codes
PP1_Moderate
This variant has been reported to segregate with FAP in > 10 affected meioses in 1 family (PP1_Moderate; PMID 1324223).
PS4
This variant has been reported in > 8 probands meeting phenotypic criteria, resulting in a total phenotype score of 5 (PS4, PMID 1324223, Ambry Genetics, Invitae, Leiden, Bonn, Melbourne internal data).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
PVS1
The c.509_512del p.(Asp170Valfs*4) (NM_000038.6) variant in APC is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 5 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).
Curation History
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