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.1746A>G (p.Glu582=)

CA10578326

231116 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 952838c6-8886-4533-8058-ef40f2af56c4

Approved on: 2023-02-19

Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.1746A>G

NM_000038.6(APC):c.1746A>G (p.Glu582=)

NC_000005.10:g.112834953A>G

CM000667.2:g.112834953A>G

NC_000005.9:g.112170650A>G

CM000667.1:g.112170650A>G

NC_000005.8:g.112198549A>G

NG_008481.4:g.147433A>G

ENST00000257430.9:c.1746A>G

ENST00000257430.8:c.1746A>G

ENST00000502371.2:n.99A>G

ENST00000504915.2:n.435A>G

ENST00000507379.5:c.1692A>G

ENST00000508376.6:c.1746A>G

ENST00000508624.5:c.*1068A>G

ENST00000512211.6:c.1746A>G

ENST00000520401.1:n.230+5981A>G

NM_000038.5:c.1746A>G

NM_001127510.2:c.1746A>G

NM_001127511.2:c.1692A>G

NM_001354895.1:c.1746A>G

NM_001354896.1:c.1800A>G

NM_001354897.1:c.1776A>G

NM_001354898.1:c.1671A>G

NM_001354899.1:c.1662A>G

NM_001354900.1:c.1623A>G

NM_001354901.1:c.1569A>G

NM_001354902.1:c.1473A>G

NM_001354903.1:c.1443A>G

NM_001354904.1:c.1368A>G

NM_001354905.1:c.1266A>G

NM_001354906.1:c.897A>G

NM_001127510.3:c.1746A>G

NM_001127511.3:c.1692A>G

NM_001354895.2:c.1746A>G

NM_001354896.2:c.1800A>G

NM_001354897.2:c.1776A>G

NM_001354898.2:c.1671A>G

NM_001354899.2:c.1662A>G

NM_001354900.2:c.1623A>G

NM_001354901.2:c.1569A>G

NM_001354902.2:c.1473A>G

NM_001354903.2:c.1443A>G

NM_001354904.2:c.1368A>G

NM_001354905.2:c.1266A>G

NM_001354906.2:c.897A>G

Benign

BS2 BS1 BP4 BP7

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.1746A>G (p.Glu582=) variant in APC is a synonymous (silent) variant that is not predicted to impact splicing (BP4, BP7). This variant has been observed in a heterozygous state in 12 unrelated healthy adult individuals worth 12 (≥ 10) healthy individual points in total (BS2; Ambry internal data). The highest population minor allele frequency of this variant in gnomAD v2.1.1 (non-cancer) is 0.0001148 in African/African American population, which is higher than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis threshold (≥ 0.0001) for BS1, and therefore meets this criterion (BS1). 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 ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: BS1, BS2, BP4, and BP7 (VCEP specifications version 1; date of approval: 12/12/2022).

BS2

This variant has been observed in heterozygous state in 12 healthy unrelated adult individuals worth 12 (≥ 10) healthy individual points in total (BS2; Ambry internal data).

BS1

The highest population minor allele frequency of the variant c.1746A>G in gnomAD v2.1.1 (non-cancer) is 0.0001148 (1/8712 alleles) in African/African American population, which is higher than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis threshold threshold (≥ 0.0001) for BS1, and therefore meets this criterion (BS1).

BP4

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

BP7

The c.1746A>G (p.Glu582=) variant is a synonymous (silent) variant that is not predicted by MaxEntScan, SpliceAI and varSEAK to impact splicing (BP4, BP7).

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