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 label mismatch: APC vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000038.6(APC):c.471G>A (p.Trp157Ter)

CA16022351

411479 (ClinVar)

Gene: APC
Condition: familial adenomatous polyposis 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 96c7f383-d44d-482e-83a5-faa8402c1404
Approved on: 2025-05-19
Published on: 2025-05-19

HGVS expressions

NM_000038.6:c.471G>A
NM_000038.6(APC):c.471G>A (p.Trp157Ter)
NC_000005.10:g.112775677G>A
CM000667.2:g.112775677G>A
NC_000005.9:g.112111374G>A
CM000667.1:g.112111374G>A
NC_000005.8:g.112139273G>A
NG_008481.4:g.88157G>A
ENST00000502371.3:c.471G>A
ENST00000504915.3:c.471G>A
ENST00000505084.2:n.527G>A
ENST00000505350.2:c.*477G>A
ENST00000507379.6:c.501G>A
ENST00000509732.6:c.471G>A
ENST00000512211.7:c.471G>A
ENST00000257430.9:c.471G>A
ENST00000257430.8:c.471G>A
ENST00000507379.5:c.501G>A
ENST00000508376.6:c.471G>A
ENST00000508624.5:c.471G>A
ENST00000512211.6:c.471G>A
NM_000038.5:c.471G>A
NM_001127510.2:c.471G>A
NM_001127511.2:c.501G>A
NM_001354895.1:c.471G>A
NM_001354896.1:c.471G>A
NM_001354897.1:c.501G>A
NM_001354898.1:c.396G>A
NM_001354899.1:c.471G>A
NM_001354900.1:c.294G>A
NM_001354901.1:c.294G>A
NM_001354902.1:c.501G>A
NM_001354903.1:c.471G>A
NM_001354904.1:c.396G>A
NM_001354905.1:c.294G>A
NM_001354906.1:c.-565G>A
NM_001127510.3:c.471G>A
NM_001127511.3:c.501G>A
NM_001354895.2:c.471G>A
NM_001354896.2:c.471G>A
NM_001354897.2:c.501G>A
NM_001354898.2:c.396G>A
NM_001354899.2:c.471G>A
NM_001354900.2:c.294G>A
NM_001354901.2:c.294G>A
NM_001354902.2:c.501G>A
NM_001354903.2:c.471G>A
NM_001354904.2:c.396G>A
NM_001354905.2:c.294G>A
NM_001354906.2:c.-565G>A
More

Pathogenic

Met criteria codes 3
PS4_Supporting PM2_Supporting PVS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for APC Version 2.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP
The NM_000038.6(APC):c.471G>A (p.Trp157Ter) variant in APC is a nonsense 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). The total minor allele frequency in gnomAD v2.1.1 (non-cancer) is 0.000004 (1/233100 alleles), which is lower than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP (HCCP VCEP) threshold of < 0.001% (0.00001) for PM2_Supporting if the allele count is ≤ 1 and therefore meets this criterion (PM2_Supporting). This variant has been reported in 1 proband meeting phenotypic criteria, resulting in a total phenotype score of 1.0 (PS4_Supporting, PMID: 20399906). Moreover, the variant has been reported in at least 4 additional probands with a colorectal cancer/polyposis associated phenotype not meeting phenotypic criteria (PMID: 22941256, 8381580, 20685668; ClinVar ID: VCV000411479.17). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal-dominant inherited FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: criteria PVS1, PS4_Supporting and PM2_Supporting applied (VCEP specifications version 2.0.3; date of approval: 7/24/2023).
Met criteria codes
PS4_Supporting
This variant has been reported in 1 proband meeting phenotypic criteria, resulting in a total phenotype score of 1.0 (PS4_Supporting, PMID: 20399906). Moreover, the variant has been reported in at least 4 additional probands with a colorectal cancer/polyposis associated phenotype not meeting phenotypic criteria (PMID: 22941256, 8381580, 20685668; ClinVar ID: VCV000411479.17).
PM2_Supporting
The total minor allele frequency in gnomAD v2.1.1 (non-cancer) is 0.000004 (1/233100 alleles), which is lower than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP (HCCP VCEP) threshold of < 0.001% (0.00001) for PM2_Supporting if the allele count is ≤ 1 and therefore meets this criterion (PM2_Supporting).
PVS1
The NM_000038.6(APC):c.471G>A (p.Trp157Ter) variant in APC is a nonsense 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).
Curation History
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