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.422G>C (p.Arg141Thr)

CA16022246

1056286 (ClinVar)

Gene: APC (HGNC:324)

Condition: familial adenomatous polyposis 1 (MONDO:0021056)

Inheritance Mode: Autosomal dominant inheritance

UUID: dc4d6a80-eb3a-4ce3-a2a5-bea49c46ee55

Approved on: 2025-05-19

Published on: 2025-05-19

HGVS expressions

NM_000038.6:c.422G>C

NM_000038.6(APC):c.422G>C (p.Arg141Thr)

NC_000005.10:g.112767390G>C

CM000667.2:g.112767390G>C

NC_000005.9:g.112103087G>C

CM000667.1:g.112103087G>C

NC_000005.8:g.112130986G>C

NG_008481.4:g.79870G>C

ENST00000502371.3:c.422G>C

ENST00000504915.3:c.422G>C

ENST00000505084.2:n.478G>C

ENST00000505350.2:c.*428G>C

ENST00000507379.6:c.452G>C

ENST00000509732.6:c.422G>C

ENST00000512211.7:c.422G>C

ENST00000257430.9:c.422G>C

ENST00000257430.8:c.422G>C

ENST00000507379.5:c.452G>C

ENST00000508376.6:c.422G>C

ENST00000508624.5:c.422G>C

ENST00000512211.6:c.422G>C

NM_000038.5:c.422G>C

NM_001127510.2:c.422G>C

NM_001127511.2:c.452G>C

NM_001354895.1:c.422G>C

NM_001354896.1:c.422G>C

NM_001354897.1:c.452G>C

NM_001354898.1:c.347G>C

NM_001354899.1:c.422G>C

NM_001354900.1:c.245G>C

NM_001354901.1:c.245G>C

NM_001354902.1:c.452G>C

NM_001354903.1:c.422G>C

NM_001354904.1:c.347G>C

NM_001354905.1:c.245G>C

NM_001354906.1:c.-614G>C

NM_001127510.3:c.422G>C

NM_001127511.3:c.452G>C

NM_001354895.2:c.422G>C

NM_001354896.2:c.422G>C

NM_001354897.2:c.452G>C

NM_001354898.2:c.347G>C

NM_001354899.2:c.422G>C

NM_001354900.2:c.245G>C

NM_001354901.2:c.245G>C

NM_001354902.2:c.452G>C

NM_001354903.2:c.422G>C

NM_001354904.2:c.347G>C

NM_001354905.2:c.245G>C

NM_001354906.2:c.-614G>C

Uncertain Significance

PM2_Supporting PVS1_Strong

BS2 PS4

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.422G>C (p.Arg141Thr) variant in APC is a G to non-G change at the last nucleotide of exon 4. It is predicted to cause skipping of exon 4, resulting in a frameshift in a gene in which loss-of-function is an established disease mechanism (PVS1_Strong). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant has been reported in 1 proband meeting phenotypic criteria, resulting in a phenotype score of 0.5 points (Invitae, internal data) (PS4 not applicable). Moreover, the variant has been observed in heterozygous state in two individuals without a colorectal cancer/polyposis associated phenotype, worth 1 healthy individual point in total (BS2_Supporting not met; [Ambry Genetics, internal data]). In summary, this variant is a variant of uncertain significance (VUS) 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_Strong and PM2_Supporting applied (VCEP specifications v2.0.3; date of approval 7/24/2023).

PM2_Supporting

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

PVS1_Strong

BS2

Moreover, the variant has been observed in heterozygous state in two individuals without a colorectal cancer/polyposis associated phenotype, worth 1 healthy individual point in total (BS2_Supporting not met; [Ambry Genetics, internal data]).

PS4

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

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.