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.3077A>C (p.Asn1026Thr)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA16028070

428167 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 49416799-184f-4974-afa9-85953582657d

Approved on: 2023-02-25

Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.3077A>C

NM_000038.6(APC):c.3077A>C (p.Asn1026Thr)

NC_000005.10:g.112838671A>C

CM000667.2:g.112838671A>C

NC_000005.9:g.112174368A>C

CM000667.1:g.112174368A>C

NC_000005.8:g.112202267A>C

NG_008481.4:g.151151A>C

ENST00000257430.9:c.3077A>C

ENST00000257430.8:c.3077A>C

ENST00000502371.2:n.1430A>C

ENST00000507379.5:c.3023A>C

ENST00000508376.6:c.3077A>C

ENST00000508624.5:c.*2399A>C

ENST00000512211.6:c.3077A>C

ENST00000520401.1:n.230+9699A>C

NM_000038.5:c.3077A>C

NM_001127510.2:c.3077A>C

NM_001127511.2:c.3023A>C

NM_001354895.1:c.3077A>C

NM_001354896.1:c.3131A>C

NM_001354897.1:c.3107A>C

NM_001354898.1:c.3002A>C

NM_001354899.1:c.2993A>C

NM_001354900.1:c.2954A>C

NM_001354901.1:c.2900A>C

NM_001354902.1:c.2804A>C

NM_001354903.1:c.2774A>C

NM_001354904.1:c.2699A>C

NM_001354905.1:c.2597A>C

NM_001354906.1:c.2228A>C

NM_001127510.3:c.3077A>C

NM_001127511.3:c.3023A>C

NM_001354895.2:c.3077A>C

NM_001354896.2:c.3131A>C

NM_001354897.2:c.3107A>C

NM_001354898.2:c.3002A>C

NM_001354899.2:c.2993A>C

NM_001354900.2:c.2954A>C

NM_001354901.2:c.2900A>C

NM_001354902.2:c.2804A>C

NM_001354903.2:c.2774A>C

NM_001354904.2:c.2699A>C

NM_001354905.2:c.2597A>C

NM_001354906.2:c.2228A>C

Uncertain Significance

PM5_Supporting PM2_Supporting PS4_Supporting

BP4 BP1

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.3077A>C variant in APC is a missense variant predicted to cause the substitution of asparagine by threonine at amino acid position 1026 (p.Asn1026Thr). This variant has been reported in 3 probands with FAP worth 1.5 phenotype points (PS4_Supporting; Ambry Internal Data). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). Another missense variant, c.3077A>G (p.Asn1026Ser) in the same codon has been classified as Likely Pathogenic for FAP by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (HCCP VCEP) (PM5_Supporting; PMID 18166348). In summary, due to insufficient evidence, this variant is a Variant of Uncertain Significance for FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: PS4_Supporting, PM2_Supporting, and PM5_Supporting (VCEP specifications version 1; date of approval: 12/12/2022).

PM5_Supporting

Another missense variant, c.3077A>G (p.Asn1026Ser) in the same codon has been classified as Likely Pathogenic for familial adenomatous polyposis by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP (PM5_supporting).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

PS4_Supporting

This variant has been reported in 3 families with familial adenomatous polyposis worth 1.5 phenotype points (PS4_Supporting; Ambry Internal Data).

BP4

The computational splicing predictor SpliceAI gives a score of 0.0 for all donor/acceptor gains and losses suggesting that the variant has no impact on splicing (BP4-not applied but reviewed to confirm lack of predicted splice defect).

BP1

APC, in which the variant was identified, is defined by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP as a gene for which primarily truncating variants are known to cause disease; however this alteration occurs at an amino acid position where other likely pathogenic alteration(s) are known (BP1-not met).

Curation History

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