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]

Variant: NM_000038.6(APC):c.2476T>G (p.Leu826Val)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA007509

142010 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ffcec97a-2384-47b7-808d-bbdfae08259c

Approved on: 2023-02-25

Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.2476T>G

NM_000038.6(APC):c.2476T>G (p.Leu826Val)

NC_000005.10:g.112838070T>G

CM000667.2:g.112838070T>G

NC_000005.9:g.112173767T>G

CM000667.1:g.112173767T>G

NC_000005.8:g.112201666T>G

NG_008481.4:g.150550T>G

ENST00000257430.9:c.2476T>G

ENST00000257430.8:c.2476T>G

ENST00000502371.2:n.829T>G

ENST00000507379.5:c.2422T>G

ENST00000508376.6:c.2476T>G

ENST00000508624.5:c.*1798T>G

ENST00000512211.6:c.2476T>G

ENST00000520401.1:n.230+9098T>G

NM_000038.5:c.2476T>G

NM_001127510.2:c.2476T>G

NM_001127511.2:c.2422T>G

NM_001354895.1:c.2476T>G

NM_001354896.1:c.2530T>G

NM_001354897.1:c.2506T>G

NM_001354898.1:c.2401T>G

NM_001354899.1:c.2392T>G

NM_001354900.1:c.2353T>G

NM_001354901.1:c.2299T>G

NM_001354902.1:c.2203T>G

NM_001354903.1:c.2173T>G

NM_001354904.1:c.2098T>G

NM_001354905.1:c.1996T>G

NM_001354906.1:c.1627T>G

NM_001127510.3:c.2476T>G

NM_001127511.3:c.2422T>G

NM_001354895.2:c.2476T>G

NM_001354896.2:c.2530T>G

NM_001354897.2:c.2506T>G

NM_001354898.2:c.2401T>G

NM_001354899.2:c.2392T>G

NM_001354900.2:c.2353T>G

NM_001354901.2:c.2299T>G

NM_001354902.2:c.2203T>G

NM_001354903.2:c.2173T>G

NM_001354904.2:c.2098T>G

NM_001354905.2:c.1996T>G

NM_001354906.2:c.1627T>G

Benign

BP1 BA1

BS1 BP4 PM2 PP3

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.2476T>G variant in APC is a missense variant predicted to cause a substitution of leucine by valine at amino acid position 826 (p.Leu826Val). The highest population minor allele frequency in gnomAD v2.1.1 is 0.1576% in the non-cancer African/African American population, which is higher than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation threshold (>0.1%) for BA1, and therefore meets this criterion (BA1). Additionally, APC is defined by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel as a gene for which primarily truncating variants are known to cause disease (BP1). Multiple lines of computational evidence suggest no splicing impact. In summary, this variant meets the criteria to be classified as Benign for FAP. ACMG/AMP criteria applied, as specified by the ClinGen/InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel: BA1, BP1 (VCEP specifications version 1; date of approval: 12/12/2022).

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).

BA1

The highest population minor allele frequency in gnomAD v2.1.1 is 0.1576% in African/African American population, which is higher than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation threshold (>0.1%) for BA1, and therefore meets this criterion (BA1).

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP3

Multiple lines of computational evidence suggest no splicing impact (SpliceAI and varSEAK).

Curation History

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