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.933G>C (p.Lys311Asn)

CA16023349

1025291 (ClinVar)

Gene: APC (HGNC:324)

Condition: familial adenomatous polyposis 1 (MONDO:0021056)

Inheritance Mode: Autosomal dominant inheritance

UUID: 25c5fc2f-b417-4d43-a9cb-4a31806c7e0c

Approved on: 2025-05-16

Published on: 2025-05-16

HGVS expressions

NM_000038.6:c.933G>C

NM_000038.6(APC):c.933G>C (p.Lys311Asn)

NC_000005.10:g.112815593G>C

CM000667.2:g.112815593G>C

NC_000005.9:g.112151290G>C

CM000667.1:g.112151290G>C

NC_000005.8:g.112179189G>C

NG_008481.4:g.128073G>C

ENST00000502371.3:c.933G>C

ENST00000504915.3:c.933G>C

ENST00000505084.2:n.989G>C

ENST00000505350.2:c.*939G>C

ENST00000507379.6:c.879G>C

ENST00000509732.6:c.933G>C

ENST00000512211.7:c.933G>C

ENST00000257430.9:c.933G>C

ENST00000257430.8:c.933G>C

ENST00000507379.5:c.879G>C

ENST00000508376.6:c.933G>C

ENST00000508624.5:c.*255G>C

ENST00000512211.6:c.933G>C

NM_000038.5:c.933G>C

NM_001127510.2:c.933G>C

NM_001127511.2:c.879G>C

NM_001354895.1:c.933G>C

NM_001354896.1:c.933G>C

NM_001354897.1:c.963G>C

NM_001354898.1:c.858G>C

NM_001354899.1:c.849G>C

NM_001354900.1:c.756G>C

NM_001354901.1:c.756G>C

NM_001354902.1:c.963G>C

NM_001354903.1:c.933G>C

NM_001354904.1:c.858G>C

NM_001354905.1:c.756G>C

NM_001354906.1:c.84G>C

NM_001127510.3:c.933G>C

NM_001127511.3:c.879G>C

NM_001354895.2:c.933G>C

NM_001354896.2:c.933G>C

NM_001354897.2:c.963G>C

NM_001354898.2:c.858G>C

NM_001354899.2:c.849G>C

NM_001354900.2:c.756G>C

NM_001354901.2:c.756G>C

NM_001354902.2:c.963G>C

NM_001354903.2:c.933G>C

NM_001354904.2:c.858G>C

NM_001354905.2:c.756G>C

NM_001354906.2:c.84G>C

Likely Pathogenic

PS4_Supporting PM2_Supporting PVS1_Strong

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.933G>C variant in APC is a G to non-G change at the last nucleotide of exon 9. RNA analysis demonstrated that the variant impacts splicing by an insertion of the first 66 nucleotides of intron 9, resulting in a premature stop codon (r.933_934ins933+1_933+66 p.K311_V312insVTEDYKPWSLMP*) (internal data Ambry Genetics; in Fig. 1B of the ACMG/AMP criteria specification by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP [HCCP VCEP] the variant was evaluated as PVS1_Supporting, but based on the additional RNA data the HCCP VCEP considers PVS1_Strong as applicable for this variant). This variant has been reported in 2 probands meeting phenotypic criteria, resulting in a total phenotype score of 1.5 (PS4_Supporting, PMID: 20685668, internal data Labcorp Genetics [formerly Invitae]). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal-dominant inherited FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: PVS1_Strong, PS4_Supporting, PM2_Supporting applied (VCEP specifications version v2.0.3; date of approval 7/24/2023).

PS4_Supporting

This variant has been reported in 2 probands meeting phenotypic criteria, resulting in a total phenotype score of 1.5 (PS4_Supporting, PMID: 20685668, internal data Labcorp Genetics [formerly Invitae]).

PM2_Supporting

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

PVS1_Strong

RNA analysis demonstrated that the variant impacts splicing by an insertion of the first 66 nucleotides of intron 9, resulting in a premature stop codon (r.933_934ins933+1_933+66 p.K311_V312insVTEDYKPWSLMP*) (internal data Ambry Genetics; in Fig. 1B of the ACMG/AMP criteria specification by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP [HCCP VCEP] the variant was evaluated as PVS1_Supporting, but based on the additional RNA data the HCCP VCEP considers PVS1_Strong as applicable for this variant).

Curation History

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