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.531+5G>C

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10602909

279681 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 5fdcb6fa-fbb5-4edb-96fc-6fc45c078785

Approved on: 2025-05-15

Published on: 2025-05-19

HGVS expressions

NM_000038.6:c.531+5G>C

NM_000038.6(APC):c.531+5G>C

NC_000005.10:g.112775742G>C

CM000667.2:g.112775742G>C

NC_000005.9:g.112111439G>C

CM000667.1:g.112111439G>C

NC_000005.8:g.112139338G>C

NG_008481.4:g.88222G>C

ENST00000502371.3:c.531+5G>C

ENST00000504915.3:c.531+5G>C

ENST00000505084.2:n.587+5G>C

ENST00000505350.2:c.*537+5G>C

ENST00000507379.6:c.561+5G>C

ENST00000509732.6:c.531+5G>C

ENST00000512211.7:c.531+5G>C

ENST00000257430.9:c.531+5G>C

ENST00000257430.8:c.531+5G>C

ENST00000507379.5:c.561+5G>C

ENST00000508376.6:c.531+5G>C

ENST00000508624.5:c.531+5G>C

ENST00000512211.6:c.531+5G>C

NM_000038.5:c.531+5G>C

NM_001127510.2:c.531+5G>C

NM_001127511.2:c.561+5G>C

NM_001354895.1:c.531+5G>C

NM_001354896.1:c.531+5G>C

NM_001354897.1:c.561+5G>C

NM_001354898.1:c.456+5G>C

NM_001354899.1:c.531+5G>C

NM_001354900.1:c.354+5G>C

NM_001354901.1:c.354+5G>C

NM_001354902.1:c.561+5G>C

NM_001354903.1:c.531+5G>C

NM_001354904.1:c.456+5G>C

NM_001354905.1:c.354+5G>C

NM_001354906.1:c.-505+5G>C

NM_001127510.3:c.531+5G>C

NM_001127511.3:c.561+5G>C

NM_001354895.2:c.531+5G>C

NM_001354896.2:c.531+5G>C

NM_001354897.2:c.561+5G>C

NM_001354898.2:c.456+5G>C

NM_001354899.2:c.531+5G>C

NM_001354900.2:c.354+5G>C

NM_001354901.2:c.354+5G>C

NM_001354902.2:c.561+5G>C

NM_001354903.2:c.531+5G>C

NM_001354904.2:c.456+5G>C

NM_001354905.2:c.354+5G>C

NM_001354906.2:c.-505+5G>C

Likely Pathogenic

PM2_Supporting PS3 PP3 PS4_Supporting

Evidence Links 1

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.531+5G>C variant in APC is an intronic variant which is located at the 5th nucleotide in intron 5. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant has been reported in 2 families meeting phenotypic criteria, resulting in a total phenotype score of 1 point (PMID: 19196998, 20223039, 12010888; the first two references refer to the same German family) (PS4_Supporting). The results from ≥ 2 in silico splicing predictors (SpliceAI and MaxEntScan) indicate that this variant may affect splicing by disrupting the donor splice site of intron 5 of APC (PP3). RNA studies have demonstrated that this variant causes exon 5 deletion (c.531+5G>C; r.423_531del; p.Arg144Serfs*8; PMID: 19196998) (PS3). 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: PS3, PS4_Supporting, PM2_Supporting and PP3 (VCEP specifications version 2.1.0; date of approval: 11/24/2023).

PM2_Supporting

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

PS3

RNA studies have demonstrated that this variant causes exon 5 deletion (c.531+5G>C; r.423_531del; p.Arg144Serfs*8; PMID: 19196998) (PS3).

RNA studies have demonstrated that this variant causes exon 5 deletion (c.531 + 5G>C; r.423_531del; p.Arg144SerfsX8; PMID: 19196998) (PS3_Very Strong). PubMed:19196998

PP3

The results from ≥ 2 in silico splicing predictors (SpliceAI and MaxEntScan) indicate that this variant may affect splicing by disrupting the donor splice site of intron 5 of APC (PP3).

PS4_Supporting

This variant has been reported in 2 families meeting phenotypic criteria, resulting in a total phenotype score of 1 point (PMID: 19196998, 20223039, 12010888; the first two references refer to the same German family) (PS4_Supporting).

Curation History

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