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.123A>G (p.Ala41=)

CA445752659

631238 (ClinVar)

Gene: APC (HGNC:324)

Condition: familial adenomatous polyposis 1 (MONDO:0021056)

Inheritance Mode: Autosomal dominant inheritance

UUID: e979db2a-db6d-41d1-8719-f439c8a6f20c

Approved on: 2023-02-18

Published on: 2023-03-14

HGVS expressions

NM_000038.6(APC):c.123A>G (p.Ala41=)

NM_000038.6:c.123A>G

NC_000005.10:g.112755013A>G

CM000667.2:g.112755013A>G

NC_000005.9:g.112090710A>G

CM000667.1:g.112090710A>G

NC_000005.8:g.112118609A>G

NG_008481.4:g.67493A>G

ENST00000257430.9:c.123A>G

ENST00000257430.8:c.123A>G

ENST00000505350.1:c.*129A>G

ENST00000507379.5:c.166-11313A>G

ENST00000508376.6:c.123A>G

ENST00000508624.5:c.123A>G

ENST00000509732.5:c.123A>G

ENST00000512211.6:c.123A>G

NM_000038.5:c.123A>G

NM_001127510.2:c.123A>G

NM_001127511.2:c.166-11313A>G

NM_001354895.1:c.123A>G

NM_001354896.1:c.123A>G

NM_001354897.1:c.166-11313A>G

NM_001354898.1:c.61-11313A>G

NM_001354899.1:c.123A>G

NM_001354900.1:c.-42-11313A>G

NM_001354901.1:c.-42-11313A>G

NM_001354902.1:c.166-11313A>G

NM_001354903.1:c.123A>G

NM_001354904.1:c.61-11313A>G

NM_001354905.1:c.-42-11313A>G

NM_001354906.1:c.-913A>G

NM_001127510.3:c.123A>G

NM_001127511.3:c.166-11313A>G

NM_001354895.2:c.123A>G

NM_001354896.2:c.123A>G

NM_001354897.2:c.166-11313A>G

NM_001354898.2:c.61-11313A>G

NM_001354899.2:c.123A>G

NM_001354900.2:c.-42-11313A>G

NM_001354901.2:c.-42-11313A>G

NM_001354902.2:c.166-11313A>G

NM_001354903.2:c.123A>G

NM_001354904.2:c.61-11313A>G

NM_001354905.2:c.-42-11313A>G

NM_001354906.2:c.-913A>G

Likely Benign

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

PM2_Supporting BP4 BP7

BS2

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.123A>G (p.Ala41=) variant in APC is synonymous (silent) variant that is not predicted by SpliceAI and VarSEAK to impact splicing (BP4 and BP7 met). This variant is absent from gnomAD v2.1.1 (PM2_supporting). This variant has been observed in heterozygous state in 1 healthy adult individual worth 0.5 healthy individual points in total (BS2_supporting not met; 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: BP4, BP7 (VCEP specifications version 1; date of approval 12/12/2022).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_supporting).

BP4

The c.123A>G (p.Ala41=) variant in APC is synonymous (silent) variant that is not predicted by SpliceAI and VarSEAK to impact splicing (BP4 and BP7 met).

BP7

The c.123A>G (p.Ala41=) variant in APC is synonymous (silent) variant that is not predicted by SpliceAI and VarSEAK to impact splicing (BP4 and BP7 met).

BS2

This variant has been observed in heterozygous state in 1 healthy unrelated adult individuals worth 0.5 healthy individual points in total (BS2_supporting not met; Invitae internal data).

Curation History

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