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.1312+5G>C

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10588378

265372 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 45e51f78-6174-4da9-8b3b-8149f0e60efb

Approved on: 2025-05-16

Published on: 2025-05-16

HGVS expressions

NM_000038.6:c.1312+5G>C

NM_000038.6(APC):c.1312+5G>C

NC_000005.10:g.112819349G>C

CM000667.2:g.112819349G>C

NC_000005.9:g.112155046G>C

CM000667.1:g.112155046G>C

NC_000005.8:g.112182945G>C

NG_008481.4:g.131829G>C

ENST00000502371.3:c.1312+5G>C

ENST00000504915.3:c.1312+5G>C

ENST00000505084.2:n.1368+5G>C

ENST00000505350.2:c.*1318+5G>C

ENST00000507379.6:c.1258+5G>C

ENST00000509732.6:c.1312+5G>C

ENST00000512211.7:c.1312+5G>C

ENST00000257430.9:c.1312+5G>C

ENST00000257430.8:c.1312+5G>C

ENST00000507379.5:c.1258+5G>C

ENST00000508376.6:c.1312+5G>C

ENST00000508624.5:c.*634+5G>C

ENST00000512211.6:c.1312+5G>C

NM_000038.5:c.1312+5G>C

NM_001127510.2:c.1312+5G>C

NM_001127511.2:c.1258+5G>C

NM_001354895.1:c.1312+5G>C

NM_001354896.1:c.1312+5G>C

NM_001354897.1:c.1342+5G>C

NM_001354898.1:c.1237+5G>C

NM_001354899.1:c.1228+5G>C

NM_001354900.1:c.1135+5G>C

NM_001354901.1:c.1135+5G>C

NM_001354902.1:c.1039+5G>C

NM_001354903.1:c.1009+5G>C

NM_001354904.1:c.934+5G>C

NM_001354905.1:c.832+5G>C

NM_001354906.1:c.463+5G>C

NM_001127510.3:c.1312+5G>C

NM_001127511.3:c.1258+5G>C

NM_001354895.2:c.1312+5G>C

NM_001354896.2:c.1312+5G>C

NM_001354897.2:c.1342+5G>C

NM_001354898.2:c.1237+5G>C

NM_001354899.2:c.1228+5G>C

NM_001354900.2:c.1135+5G>C

NM_001354901.2:c.1135+5G>C

NM_001354902.2:c.1039+5G>C

NM_001354903.2:c.1009+5G>C

NM_001354904.2:c.934+5G>C

NM_001354905.2:c.832+5G>C

NM_001354906.2:c.463+5G>C

Likely Pathogenic

PM2_Supporting PS1_Moderate PS4_Moderate PP3

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.1312+5G>C variant in APC is an intronic variant which is located at the 5th nucleotide in intron 10. This variant has been reported in 3 probands meeting phenotypic criteria, resulting in a total phenotype score of 2.5 points (PS4_Moderate, Ambry Genetics, GeneDx, Invitae internal data). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The results from two in silico splicing predictors (SpliceAI and MaxEntScan) indicate that this variant may affect splicing by disrupting the donor splice site of intron 10 of APC (PP3). Moreover, this variant has similar in silico predictions compared to another non-canonical splicing variant at that same nucleotide position (c.1312+5G>A) which is classified as Likely Pathogenic for FAP by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP (HCCP VCEP) (PS1_Moderate). 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 HCCP VCEP: PP3, PS1_Moderate, PS4_Moderate, PM2_Supporting (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).

PS1_Moderate

This variant has similar in silico predictions compared to another non-canonical splicing variant at that same nucleotide position (c.1312+5G>A) which is classified as Likely Pathogenic for FAP by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP (HCCP VCEP) (PS1_Moderate).

PS4_Moderate

This variant has been reported in 3 probands meeting phenotypic criteria, resulting in a total phenotype score of 2.5 points (PS4_Moderate, Ambry Genetics, GeneDx, Invitae internal data).

PP3

The results from two in silico splicing predictors (SpliceAI and MaxEntScan) indicate that this variant may affect splicing by disrupting the donor splice site of intron 10 of APC (PP3).

Curation History

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