Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000038.6(APC):c.8514C>A (p.Tyr2838Ter)

CA16039798

486740 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 5ffbd0dd-034a-48a6-a96c-00b28ed9808f

Approved on: 2023-02-26

Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.8514C>A

NM_000038.6(APC):c.8514C>A (p.Tyr2838Ter)

NC_000005.10:g.112844108C>A

CM000667.2:g.112844108C>A

NC_000005.9:g.112179805C>A

CM000667.1:g.112179805C>A

NC_000005.8:g.112207704C>A

NG_008481.4:g.156588C>A

ENST00000257430.9:c.8514C>A

ENST00000257430.8:c.8514C>A

ENST00000508376.6:c.8514C>A

ENST00000520401.1:n.231-12541C>A

NM_000038.5:c.8514C>A

NM_001127510.2:c.8514C>A

NM_001127511.2:c.8460C>A

NM_001354895.1:c.8514C>A

NM_001354896.1:c.8568C>A

NM_001354897.1:c.8544C>A

NM_001354898.1:c.8439C>A

NM_001354899.1:c.8430C>A

NM_001354900.1:c.8391C>A

NM_001354901.1:c.8337C>A

NM_001354902.1:c.8241C>A

NM_001354903.1:c.8211C>A

NM_001354904.1:c.8136C>A

NM_001354905.1:c.8034C>A

NM_001354906.1:c.7665C>A

NM_001127510.3:c.8514C>A

NM_001127511.3:c.8460C>A

NM_001354895.2:c.8514C>A

NM_001354896.2:c.8568C>A

NM_001354897.2:c.8544C>A

NM_001354898.2:c.8439C>A

NM_001354899.2:c.8430C>A

NM_001354900.2:c.8391C>A

NM_001354901.2:c.8337C>A

NM_001354902.2:c.8241C>A

NM_001354903.2:c.8211C>A

NM_001354904.2:c.8136C>A

NM_001354905.2:c.8034C>A

NM_001354906.2:c.7665C>A

Uncertain Significance

PS4_Moderate PM2_Supporting

PVS1

Evidence Links 0

Expert Panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

The c.8514C>A variant in APC is a variant predicted to cause a premature stop codon at position 2838 (p.Tyr2838*) in exon 16, downstream of codon 2645. As a result, the PVS1 rule is not applicable. This variant has been reported in 2 probands meeting phenotype criteria, resulting in a total phenotype score of 2 (PS4_moderate, Ambry and Invitae internal data). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this is a Variant of Unknown Significance (VUS) for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: PS4_moderate and PM2_supporting. (VCEP specifications version 1; date of approval: 12/12/2022).

PS4_Moderate

This variant has been reported in 1 proband meeting ≥ 20 colorectal adenomas 20-70 yr (0.5p) and typical FAP family history (0.5p), 1 proband meeting ≥ 20 colorectal adenomas 20-70 yr (0.5p), 1 proband meeting ≥ 20 colorectal adenomas 20-70 yr (0.5p), resulting in a total phenotype score of 2 (PS4_moderate, Ambry and Invitae).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

PVS1

N/A - Variants introducing a frameshift and/or premature truncation codon upstream of codon 49 and downstream of codon 2645.

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