Evidence Repository - GenboreeKB

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.3083G>A (p.Ser1028Asn)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA16028084

428186 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 7cb03244-ee57-4d80-9542-a0a5abc44d98

Approved on: 2023-02-25

Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.3083G>A

NM_000038.6(APC):c.3083G>A (p.Ser1028Asn)

NC_000005.10:g.112838677G>A

CM000667.2:g.112838677G>A

NC_000005.9:g.112174374G>A

CM000667.1:g.112174374G>A

NC_000005.8:g.112202273G>A

NG_008481.4:g.151157G>A

ENST00000502371.3:c.2748G>A

ENST00000504915.3:c.3137G>A

ENST00000505350.2:c.*3089G>A

ENST00000507379.6:c.3029G>A

ENST00000509732.6:c.3083G>A

ENST00000512211.7:c.3083G>A

ENST00000257430.9:c.3083G>A

ENST00000257430.8:c.3083G>A

ENST00000502371.2:c.1436G>A

ENST00000507379.5:c.3029G>A

ENST00000508376.6:c.3083G>A

ENST00000508624.5:c.*2405G>A

ENST00000512211.6:c.3083G>A

ENST00000520401.1:c.230+9705G>A

NM_000038.5:c.3083G>A

NM_001127510.2:c.3083G>A

NM_001127511.2:c.3029G>A

NM_001354895.1:c.3083G>A

NM_001354896.1:c.3137G>A

NM_001354897.1:c.3113G>A

NM_001354898.1:c.3008G>A

NM_001354899.1:c.2999G>A

NM_001354900.1:c.2960G>A

NM_001354901.1:c.2906G>A

NM_001354902.1:c.2810G>A

NM_001354903.1:c.2780G>A

NM_001354904.1:c.2705G>A

NM_001354905.1:c.2603G>A

NM_001354906.1:c.2234G>A

NM_001127510.3:c.3083G>A

NM_001127511.3:c.3029G>A

NM_001354895.2:c.3083G>A

NM_001354896.2:c.3137G>A

NM_001354897.2:c.3113G>A

NM_001354898.2:c.3008G>A

NM_001354899.2:c.2999G>A

NM_001354900.2:c.2960G>A

NM_001354901.2:c.2906G>A

NM_001354902.2:c.2810G>A

NM_001354903.2:c.2780G>A

NM_001354904.2:c.2705G>A

NM_001354905.2:c.2603G>A

NM_001354906.2:c.2234G>A

Uncertain Significance

PS4_Supporting PP1_Moderate PM2_Supporting PM5_Supporting

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.3083G>A variant in APC is a missense variant predicted to cause the substitution of serine to asparagine at amino acid position 1028 (p.Ser1028Asn). This alteration has been identified in 2 families with attenuated FAP worth 1 phenotype points (PS4_supporting). Two other missense variants (c.3084T>A and c.3083G>T) in the same codon leading to a different amino acid change at this position (p.Ser1028Arg; p.Ser1028Ile) have been classified as Likely Pathogenic by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (PM5_Supporting). Co-segregation data shows that this variant segregated with FAP in 6 meiosis in one family (PP1_Moderate; Ambry internal data). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, due to insufficient evidence, this variant is a VUS for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis: PS4_Supporting, PM5_Supporting, PP1_Moderate and PM2_Supporting (VCEP specifications version 1; date of approval: 12/12/2022).

PS4_Supporting

Detected in cases with FAP (PMID 32750050/Ambry Genetics internal data, Invitae internal data), 1 phenotype point reached; PS4_Supporting can be applied.

PP1_Moderate

PMID: 32750050/ Ambry internal data: Variant segregates in 6 meioses in one family, PP1_Moderate can be applied.

PM2_Supporting

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

PM5_Supporting

Variant with a different missense change at p.Ser1028, NM_000038.6(APC):c.3084T>A(p.Ser1028Arg) is likely pathogenic as per APC VCEP specifications. Grantham´s distance of the currently evaluated variant is equal to the reported variant NM_000038.6(APC):c.3084T>A(p.Ser1028Arg).

Curation History

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