The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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Variant: NM_000038.6(APC):c.8438C>A (p.Thr2813Lys)

411374 (ClinVar)

Gene: APC
Condition: familial adenomatous polyposis 1
Inheritance Mode: Autosomal dominant inheritance
UUID: 2ff9d2d2-7af6-47bd-a8d7-403b111f47e6
Approved on: 2023-02-26
Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.8438C>A
NM_000038.6(APC):c.8438C>A (p.Thr2813Lys)

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"
Met criteria codes 3
PM2_Supporting BP1 BS2_Supporting
Not Met criteria codes 1
BP4

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.8438C>A variant in APC is a missense variant predicted to cause the substitution of Threonine by Lysine at amino acid position 2813 (p.Thr2813Lys). This variant has been observed in ≥ 3 individuals with no features or family history of FAP, which is worth 3 healthy individual points (BS2_supporting; Invitae and Ambry internal data). APC is defined by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (HCCP VCEP) as a gene for which primarily truncating variants are known to cause disease (BP1). This variant is absent from gnomAD v2.1.1 (PM2_supporting). In summary, this variant meets the criteria to be classified as Likely Benign for FAP. Although there are both pathogenic and benign types of evidence for this variant, the pathogenic evidence is not considered inconsistent with the final classification. ACMG/AMP criteria applied, as specified by the HCCP VCEP: BS2_supporting, and BP1. (VCEP specifications version 1; date of approval: 12/12/2022).
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_supporting).
BP1
APC, in which the variant was identified, is defined by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP as a gene for which primarily truncating variants are known to cause disease (BP1).
BS2_Supporting
The variant c.8438C>A has been observed in ≥ 3 individuals with no features or family history of FAP, a condition with full penetrance at an early age (BS2_supporting; Invitae, Ambry).
Not Met criteria codes
BP4
N/A for missense variants
Curation History
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