Evidence Repository - GenboreeKB

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>A

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA16611621

411416 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 482cc3f2-e07c-4e9b-acf9-aca73280016b

Approved on: 2025-05-15

Published on: 2025-05-19

HGVS expressions

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

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

NC_000005.10:g.112819349G>A

CM000667.2:g.112819349G>A

NC_000005.9:g.112155046G>A

CM000667.1:g.112155046G>A

NC_000005.8:g.112182945G>A

NG_008481.4:g.131829G>A

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Likely Pathogenic

PS4 PM6_Supporting PM2_Supporting PS3_Moderate

Evidence Links 3

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>A variant in APC is an intronic variant which is located at the 5th nucleotide in intron 10. This variant has been reported in 16 probands meeting phenotypic criteria, resulting in a total phenotype score of 11.5 points (internal data Labcorp Genetics [formerly Invitae], Ambry Genetics, Peter MacCallum Cancer Centre, Victoria, Australia, PMID: 15459959 and 23159591) (PS4). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). RNA studies have demonstrated that this variant causes exon 10 skipping (PMID: 22987206, 15459959, 15833136, Ambry internal data) (PS3_Moderate). This variant has been identified as a de novo occurrence with unconfirmed parental relationships in 1 individual with FAP, resulting in a total de novo score of 0.5 (PMID: 15833136) (PM6_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 ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP: PS3_Moderate, PS4, PM2_Supporting, PM6_Supporting (VCEP specifications version 2.1.0; date of approval: 11/24/2023).

PS4

This variant has been reported in 16 probands meeting phenotypic criteria, resulting in a total phenotype score of 11.5 points (internal data Labcorp Genetics [formerly Invitae], Ambry Genetics, Peter MacCallum Cancer Centre, Victoria, Australia, PMID: 15459959 and 23159591) (PS4).

PM6_Supporting

This variant has been identified as a de novo occurrence with unconfirmed parental relationships in 1 individual with FAP, resulting in a total de novo score of 0.5 (PMID: 15833136) (PM6_Supporting).

PM2_Supporting

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

PS3_Moderate

RNA studies have demonstrated that this variant causes exon 10 skipping (PMID: 22987206, 15459959, 15833136, Ambry internal data) (PS3_Moderate).

designated as IVS9+5G>A - RT-PCR was completed in this study and showed exon 9 skipping. Results in a frameshift with premature STOP codon. According to authors, the patient's pheno resembled AFAP. mutation was determined to be de novo after familial testing. PubMed:15833136

results in abberant transcript but also seen in 3 controls PubMed:22987206

transcript analysis showed this alteration led to exon 9 skipping. PubMed:15459959

Curation History

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