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.1240del (p.Arg414fs)

CA645509160

438864 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 14569ca5-59c5-46f3-9907-beb376fc4b20

Approved on: 2023-02-18

Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.1240del

NM_000038.6(APC):c.1240del (p.Arg414fs)

NC_000005.10:g.112819272del

CM000667.2:g.112819272del

NC_000005.9:g.112154969del

CM000667.1:g.112154969del

NC_000005.8:g.112182868del

NG_008481.4:g.131752del

ENST00000257430.9:c.1240del

ENST00000257430.8:c.1240del

ENST00000507379.5:c.1186del

ENST00000508376.6:c.1240del

ENST00000508624.5:c.*562del

ENST00000512211.6:c.1240del

NM_000038.5:c.1240del

NM_001127510.2:c.1240del

NM_001127511.2:c.1186del

NM_001354895.1:c.1240del

NM_001354896.1:c.1240del

NM_001354897.1:c.1270del

NM_001354898.1:c.1165del

NM_001354899.1:c.1156del

NM_001354900.1:c.1063del

NM_001354901.1:c.1063del

NM_001354902.1:c.967del

NM_001354903.1:c.937del

NM_001354904.1:c.862del

NM_001354905.1:c.760del

NM_001354906.1:c.391del

NM_001127510.3:c.1240del

NM_001127511.3:c.1186del

NM_001354895.2:c.1240del

NM_001354896.2:c.1240del

NM_001354897.2:c.1270del

NM_001354898.2:c.1165del

NM_001354899.2:c.1156del

NM_001354900.2:c.1063del

NM_001354901.2:c.1063del

NM_001354902.2:c.967del

NM_001354903.2:c.937del

NM_001354904.2:c.862del

NM_001354905.2:c.760del

NM_001354906.2:c.391del

Likely Pathogenic

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

PVS1 PM2_Supporting

PS4

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.1240del (p.Arg414Alafs*40)) variant in APC is a frameshift variant located between codon 49 and 2645 predicted to cause a premature stop codon in exon 10 in a gene in which loss-of-function is an established disease mechanism (PVS1). It is listed once each in ClinVar and the APC InSiGHT LOVD (https://www.lovd.nl/APC), without informative clinical or phenotypic data. The variant is not reported in gnomAD (PM2_supporting). In summary, this variant meets the criteria to be classified as Likely Pathogenic for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: PVS1 and PM2_Supporting (VCEP specifications version 1; date of approval: 12/12/2022).

PVS1

The c.1240del (p.Arg414fs) variant is a nonsense variant predicted to cause a premature stop codon in coding exon 10 in a gene in which loss-of-function is an established disease mechanism (PVS1).

PM2_Supporting

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

PS4

This variant has been reported in 1 proband meeting phenotypic criteria, resulting in a total phenotype score of 0.5 (PS4 not met, Bonn internal data).

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