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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000038.6(APC):c.645+9C>A

CA337726

215569 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2d4c4cc3-0913-4346-8f73-e53c6dfae5e0

Approved on: 2023-02-18

Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.645+9C>A

NM_000038.6(APC):c.645+9C>A

NC_000005.10:g.112780912C>A

CM000667.2:g.112780912C>A

NC_000005.9:g.112116609C>A

CM000667.1:g.112116609C>A

NC_000005.8:g.112144508C>A

NG_008481.4:g.93392C>A

ENST00000257430.9:c.645+9C>A

ENST00000257430.8:c.645+9C>A

ENST00000507379.5:c.675+9C>A

ENST00000508376.6:c.645+9C>A

ENST00000508624.5:c.645+9C>A

ENST00000512211.6:c.645+9C>A

NM_000038.5:c.645+9C>A

NM_001127510.2:c.645+9C>A

NM_001127511.2:c.675+9C>A

NM_001354895.1:c.645+9C>A

NM_001354896.1:c.645+9C>A

NM_001354897.1:c.675+9C>A

NM_001354898.1:c.570+9C>A

NM_001354899.1:c.645+9C>A

NM_001354900.1:c.468+9C>A

NM_001354901.1:c.468+9C>A

NM_001354902.1:c.675+9C>A

NM_001354903.1:c.645+9C>A

NM_001354904.1:c.570+9C>A

NM_001354905.1:c.468+9C>A

NM_001354906.1:c.-391+9C>A

NM_001127510.3:c.645+9C>A

NM_001127511.3:c.675+9C>A

NM_001354895.2:c.645+9C>A

NM_001354896.2:c.645+9C>A

NM_001354897.2:c.675+9C>A

NM_001354898.2:c.570+9C>A

NM_001354899.2:c.645+9C>A

NM_001354900.2:c.468+9C>A

NM_001354901.2:c.468+9C>A

NM_001354902.2:c.675+9C>A

NM_001354903.2:c.645+9C>A

NM_001354904.2:c.570+9C>A

NM_001354905.2:c.468+9C>A

NM_001354906.2:c.-391+9C>A

Likely Benign

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

BS2_Supporting BP4 BP7 PM2_Supporting

BS1 BP1 BA1 PP3

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.645+9C>A (p.?) variant in APC is an intronic variant at or beyond +7/–21 and is not predicted to impact splicing by multiple splicing predictors including SpliceAI, VarSEAK and MaxEntScan (BP4, BP7). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant has been observed in heterozygous state in 7 healthy unrelated adult individuals worth 6.5 (≥ 3) healthy individual points in total (BS2_Supporting; Ambry, Invitae internal data). In summary, this variant meets the criteria to be classified as Likely Benign for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: BS2_Supporting, BP4, and BP7 (VCEP specifications version 1.0; date of approval: 12/12/2022).

BS2_Supporting

This variant has been observed in heterozygous state in 7 healthy unrelated adult individuals worth 6.5 (≥ 3) healthy individual points in total (BS2_Supporting; Ambry, Invitae internal data).

BP4

The results from 3 in silico splicing predictors [MaxEntScan, SpliceAI, VarSeak] support that this variant does not affect splicing (BP4).

BP7

The c.645+9CA variant (NM_000038.6) is a intronic variant at or beyond +7/–21 that is not predicted by MaxEntScan, SpliceAI, or Varseak to impact splicing (BP4, BP7).

PM2_Supporting

This variant is absent from gnomAD v2.1.1

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

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