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]

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Variant: NM_000038.6(APC):c.705A>G (p.Leu235=)

CA012805

92349 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f6cb4954-a857-4ac2-a4db-5367f1a4f0d3

Approved on: 2023-02-18

Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.705A>G

NM_000038.6(APC):c.705A>G (p.Leu235=)

NC_000005.10:g.112792505A>G

CM000667.2:g.112792505A>G

NC_000005.9:g.112128202A>G

CM000667.1:g.112128202A>G

NC_000005.8:g.112156101A>G

NG_008481.4:g.104985A>G

ENST00000257430.9:c.705A>G

ENST00000257430.8:c.705A>G

ENST00000507379.5:c.676-8774A>G

ENST00000508376.6:c.705A>G

ENST00000508624.5:c.705A>G

ENST00000512211.6:c.705A>G

NM_000038.5:c.705A>G

NM_001127510.2:c.705A>G

NM_001127511.2:c.676-8774A>G

NM_001354895.1:c.705A>G

NM_001354896.1:c.705A>G

NM_001354897.1:c.735A>G

NM_001354898.1:c.630A>G

NM_001354899.1:c.646-8774A>G

NM_001354900.1:c.528A>G

NM_001354901.1:c.528A>G

NM_001354902.1:c.735A>G

NM_001354903.1:c.705A>G

NM_001354904.1:c.630A>G

NM_001354905.1:c.528A>G

NM_001354906.1:c.-331A>G

NM_001127510.3:c.705A>G

NM_001127511.3:c.676-8774A>G

NM_001354895.2:c.705A>G

NM_001354896.2:c.705A>G

NM_001354897.2:c.735A>G

NM_001354898.2:c.630A>G

NM_001354899.2:c.646-8774A>G

NM_001354900.2:c.528A>G

NM_001354901.2:c.528A>G

NM_001354902.2:c.735A>G

NM_001354903.2:c.705A>G

NM_001354904.2:c.630A>G

NM_001354905.2:c.528A>G

NM_001354906.2:c.-331A>G

Benign

BS2 BP7 BP4 BA1

BS4 BS3 BP5 BP2 PS2 PS4 PS3 PM6 PM1 PM3 PP4 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.705A>G (p.Leu235=) variant in APC is a synonymous (silent) variant that is not predicted to impact splicing by multiple splicing predictors including SpliceAI, VarSEAK and MaxEntScan (BP4, BP7). This variant has been observed 3 (≥ 2) times in homozygous state in gnomAD 2.1.1 (BS2). The highest population minor allele frequency in the non-cancer population of gnomAD v2.1.1 is 0.004669 in the Finnish population, which is higher than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (HCCP VCEP) threshold (>0.001) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as Benign for FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: BA1, BS2, BP4, and BP7 (Specification Version 1.0; date of approval: 12/12/2022).

BS2

This variant has been observed 3 (≥ 2) times in homozygous state in gnomAD 2.1.1 (BS2).

BP7

The c.705A>G (p.Leu235=) variant is a synonymous (silent) variant that is not predicted by SpliceAI and MaxEntScan to impact splicing (scores=0).

BP4

The c.705A>G (p.Leu235=) variant is a synonymous (silent) variant that is not predicted by SpliceAI, varSEAK or MaxEntScan to impact splicing (BP4, BP7).

BA1

The highest population minor allele frequency in the non-cancer population of gnomAD v2.1.1 is 0.004669 in the Finnish population, which is higher than the ClinGen APC VCEP threshold (>0.001) for BA1, and therefore meets this criterion (BA1).

BS4