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.1626+2T>G

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10578321

230944 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2807ff61-1552-482a-90b2-892d47050e14

Approved on: 2023-02-19

Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.1626+2T>G

NM_000038.6(APC):c.1626+2T>G

NC_000005.10:g.112828008T>G

CM000667.2:g.112828008T>G

NC_000005.9:g.112163705T>G

CM000667.1:g.112163705T>G

NC_000005.8:g.112191604T>G

NG_008481.4:g.140488T>G

ENST00000257430.9:c.1626+2T>G

ENST00000257430.8:c.1626+2T>G

ENST00000502371.2:n.96+6017T>G

ENST00000504915.2:n.315+2T>G

ENST00000505084.1:n.113+2T>G

ENST00000507379.5:c.1572+2T>G

ENST00000508376.6:c.1626+2T>G

ENST00000508624.5:c.*948+2T>G

ENST00000512211.6:c.1626+2T>G

ENST00000520401.1:n.113+2T>G

NM_000038.5:c.1626+2T>G

NM_001127510.2:c.1626+2T>G

NM_001127511.2:c.1572+2T>G

NM_001354895.1:c.1626+2T>G

NM_001354896.1:c.1680+2T>G

NM_001354897.1:c.1656+2T>G

NM_001354898.1:c.1551+2T>G

NM_001354899.1:c.1542+2T>G

NM_001354900.1:c.1503+2T>G

NM_001354901.1:c.1449+2T>G

NM_001354902.1:c.1353+2T>G

NM_001354903.1:c.1323+2T>G

NM_001354904.1:c.1248+2T>G

NM_001354905.1:c.1146+2T>G

NM_001354906.1:c.777+2T>G

NM_001127510.3:c.1626+2T>G

NM_001127511.3:c.1572+2T>G

NM_001354895.2:c.1626+2T>G

NM_001354896.2:c.1680+2T>G

NM_001354897.2:c.1656+2T>G

NM_001354898.2:c.1551+2T>G

NM_001354899.2:c.1542+2T>G

NM_001354900.2:c.1503+2T>G

NM_001354901.2:c.1449+2T>G

NM_001354902.2:c.1353+2T>G

NM_001354903.2:c.1323+2T>G

NM_001354904.2:c.1248+2T>G

NM_001354905.2:c.1146+2T>G

NM_001354906.2:c.777+2T>G

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

PM2_Supporting PVS1

PM6 PM3 PM1 BS4 BS3 BS2 BP5 BP2 PS2 PS3 PS4 PP1

Evidence Links 0

Expert Panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

The c.1626+2T>G variant in APC occurs within the canonical splice donor site (±1/2) of intron 13. It is predicted to cause skipping of exon 13, resulting in an in-frame deletion (removing amino acids 517-542) of an exon with sufficient supportive clinical data (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_supporting). 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: PVS1, PM2_supporting (Specification Version 1.0; date of approval: 12/12/2022).

PM2_Supporting

This variant is absent from gnomAD v2.1.1

PVS1

The c.1626+2T>G variant in APC occurs within the canonical splice donor site (+1,2) of intron 12. It is predicted to cause skipping of biologically relevant exon 12, resulting in an in-frame deletion (removes amino acids 517-542) that is predicted to escape nonsense mediated decay (PVS1). SpliceAI donor loss score=1. MaxEntScan predicts splice loss: ref (7.637) - alt (-0.011) = 7.647.

PM6