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.420G>C (p.Glu140Asp)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA008951

41529 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2e794a2d-90d8-45db-99ed-2ae3f3865213

Approved on: 2023-02-18

Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.420G>C

NM_000038.6(APC):c.420G>C (p.Glu140Asp)

NC_000005.10:g.112767388G>C

CM000667.2:g.112767388G>C

NC_000005.9:g.112103085G>C

CM000667.1:g.112103085G>C

NC_000005.8:g.112130984G>C

NG_008481.4:g.79868G>C

ENST00000257430.9:c.420G>C

ENST00000257430.8:c.420G>C

ENST00000507379.5:c.450G>C

ENST00000508376.6:c.420G>C

ENST00000508624.5:c.420G>C

ENST00000512211.6:c.420G>C

NM_000038.5:c.420G>C

NM_001127510.2:c.420G>C

NM_001127511.2:c.450G>C

NM_001354895.1:c.420G>C

NM_001354896.1:c.420G>C

NM_001354897.1:c.450G>C

NM_001354898.1:c.345G>C

NM_001354899.1:c.420G>C

NM_001354900.1:c.243G>C

NM_001354901.1:c.243G>C

NM_001354902.1:c.450G>C

NM_001354903.1:c.420G>C

NM_001354904.1:c.345G>C

NM_001354905.1:c.243G>C

NM_001354906.1:c.-616G>C

NM_001127510.3:c.420G>C

NM_001127511.3:c.450G>C

NM_001354895.2:c.420G>C

NM_001354896.2:c.420G>C

NM_001354897.2:c.450G>C

NM_001354898.2:c.345G>C

NM_001354899.2:c.420G>C

NM_001354900.2:c.243G>C

NM_001354901.2:c.243G>C

NM_001354902.2:c.450G>C

NM_001354903.2:c.420G>C

NM_001354904.2:c.345G>C

NM_001354905.2:c.243G>C

NM_001354906.2:c.-616G>C

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"

BS2 BP2 BP1 PM2_Supporting

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.420G>C variant in APC is a missense variant predicted to cause substitution of glutamic acid by aspartic acid at amino acid 140 (p.Glu140Asp). APCis 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 has been observed in heterozygous state in 67 healthy unrelated adult individuals worth ≥ 10 healthy individual points in total (BS2; Ambry Genetics, Invitae, GeneDX internal data). This variant has also been observed in trans with a variant classified as (likely) pathogenic by the HCCP VCEP in an individual with FAP (BP2; Invitae Internal Data). Finally, 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 based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: BS2, BP1, BP2 (VCEP specifications version 1; date of approval 12/12/2022).

BS2

This variant has been observed in heterozygous state in 67 healthy unrelated adult individuals worth ≥ 10 healthy individual points in total (BS2; Ambry Genetics, Invitae, GeneDX internal data).

BP2

This variant has been observed in trans with a variant classified as (likely) pathogenic by the ClinGen InSiGHT Hereditary Colorectal Cancer/ Polyposis VCEP in an individual with FAP (BP2; Invitae Internal Data).

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).

PM2_Supporting

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

Curation History

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