Variant: NM_000038.6(APC):c.4778del (p.Lys1593fs)

CA658655953

486786 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

UUID: e0829064-a90a-4c77-87cd-27b89477f04d

Approved on: 2023-02-26

Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.4778del
NM_000038.6(APC):c.4778del (p.Lys1593fs)
NC_000005.10:g.112840372del
CM000667.2:g.112840372del
NC_000005.9:g.112176069del
CM000667.1:g.112176069del
NC_000005.8:g.112203968del
NG_008481.4:g.152852del
ENST00000257430.9:c.4778del
ENST00000257430.8:c.4778del
ENST00000508376.6:c.4778del
ENST00000508624.5:c.*4100del
ENST00000520401.1:n.230+11400del
NM_000038.5:c.4778del
NM_001127510.2:c.4778del
NM_001127511.2:c.4724del
NM_001354895.1:c.4778del
NM_001354896.1:c.4832del
NM_001354897.1:c.4808del
NM_001354898.1:c.4703del
NM_001354899.1:c.4694del
NM_001354900.1:c.4655del
NM_001354901.1:c.4601del
NM_001354902.1:c.4505del
NM_001354903.1:c.4475del
NM_001354904.1:c.4400del
NM_001354905.1:c.4298del
NM_001354906.1:c.3929del
NM_001127510.3:c.4778del
NM_001127511.3:c.4724del
NM_001354895.2:c.4778del
NM_001354896.2:c.4832del
NM_001354897.2:c.4808del
NM_001354898.2:c.4703del
NM_001354899.2:c.4694del
NM_001354900.2:c.4655del
NM_001354901.2:c.4601del
NM_001354902.2:c.4505del
NM_001354903.2:c.4475del
NM_001354904.2:c.4400del
NM_001354905.2:c.4298del
NM_001354906.2:c.3929del

Pathogenic

• Met criteria codes: PS4_Supporting PVS1 PM2_Supporting

Expert Panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

Criteria Specification Information

Evidence submitted by expert panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

The c.4778del p.(Lys1593Serfs*57) 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 2 probands meeting phenotypic criteria, resulting in a total phenotype score of 1 (PS4_Supporting, Internal lab contributors). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant is classified as 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, PS4_Supporting, PM2_Supporting (VCEP specifications version 1; date of approval: 12/12/2022).

Met criteria codes

• PS4_Supporting: This variant has been reported in 2 of probands meeting phenotypic criteria, resulting in a total phenotype score of 1 (PS4_Supporting, Internal lab contributors).
• PVS1: The c.4778del p.(Lys1593Serfs*57) (NM_000038.6) variant in APC is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 16 leading to nonsense mediated decay 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).