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.4393_4394del (p.Ser1465fs)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA009520

811 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2700da46-a39e-4905-9dc3-5daef3566b0f

Approved on: 2025-05-19

Published on: 2025-05-19

HGVS expressions

NM_000038.6:c.4393_4394delAG

NM_000038.6:c.4393_4394del

NM_000038.6(APC):c.4393_4394del (p.Ser1465fs)

NC_000005.10:g.112839987_112839988del

CM000667.2:g.112839987_112839988del

NC_000005.9:g.112175684_112175685del

CM000667.1:g.112175684_112175685del

NC_000005.8:g.112203583_112203584del

NG_008481.4:g.152467_152468del

ENST00000504915.3:c.4447_4448del

ENST00000505350.2:c.*4399_*4400del

ENST00000507379.6:c.4339_4340del

ENST00000509732.6:c.4393_4394del

ENST00000512211.7:c.4393_4394del

ENST00000257430.9:c.4393_4394del

ENST00000257430.8:c.4393_4394del

ENST00000508376.6:c.4393_4394del

ENST00000508624.5:c.*3715_*3716del

ENST00000520401.1:c.230+11015_230+11016del

NM_000038.5:c.4393_4394del

NM_001127510.2:c.4393_4394del

NM_001127511.2:c.4339_4340del

NM_001354895.1:c.4393_4394del

NM_001354896.1:c.4447_4448del

NM_001354897.1:c.4423_4424del

NM_001354898.1:c.4318_4319del

NM_001354899.1:c.4309_4310del

NM_001354900.1:c.4270_4271del

NM_001354901.1:c.4216_4217del

NM_001354902.1:c.4120_4121del

NM_001354903.1:c.4090_4091del

NM_001354904.1:c.4015_4016del

NM_001354905.1:c.3913_3914del

NM_001354906.1:c.3544_3545del

NM_001127510.3:c.4393_4394del

NM_001127511.3:c.4339_4340del

NM_001354895.2:c.4393_4394del

NM_001354896.2:c.4447_4448del

NM_001354897.2:c.4423_4424del

NM_001354898.2:c.4318_4319del

NM_001354899.2:c.4309_4310del

NM_001354900.2:c.4270_4271del

NM_001354901.2:c.4216_4217del

NM_001354902.2:c.4120_4121del

NM_001354903.2:c.4090_4091del

NM_001354904.2:c.4015_4016del

NM_001354905.2:c.3913_3914del

NM_001354906.2:c.3544_3545del

Pathogenic

PVS1 PS4 PM2_Supporting

Evidence Links 0

Expert Panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

Criteria Specification Information

Criteria Specification: ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for APC Version 2.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

The NM_000038.6(APC):c.4393_4394del (p.Ser1465TrpfsTer3) variant in APC is a frameshift variant located between codon 49 and 2645 and predicted to cause a premature stop codon in exon 16 in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has been reported in 4 probands meeting 4 phenotype points (PS4_Strong, [PMID: 1316610, 28018803, 29998021, 28782241, 10768871]). The variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal-dominant inherited FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP: criteria PVS1, PS4_Strong and PM2_Supporting applied (VCEP specifications version v2.1.0; date of approval 11/24/2023).

PVS1

PS4

This variant has been reported in 4 probands meeting 4 phenotype points (PS4_Strong, [PMID: 1316610, 28018803, 29998021, 28782241, 10768871]).

PM2_Supporting

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

Curation History

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