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.3084T>G (p.Ser1028Arg)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA16028087

862543 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e7f2faf1-dc7a-40c0-9a2f-f65cf38db1d0

Approved on: 2023-02-25

Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.3084T>G

NM_000038.6(APC):c.3084T>G (p.Ser1028Arg)

NC_000005.10:g.112838678T>G

CM000667.2:g.112838678T>G

NC_000005.9:g.112174375T>G

CM000667.1:g.112174375T>G

NC_000005.8:g.112202274T>G

NG_008481.4:g.151158T>G

ENST00000257430.9:c.3084T>G

ENST00000257430.8:c.3084T>G

ENST00000502371.2:n.1437T>G

ENST00000507379.5:c.3030T>G

ENST00000508376.6:c.3084T>G

ENST00000508624.5:c.*2406T>G

ENST00000512211.6:c.3084T>G

ENST00000520401.1:n.230+9706T>G

NM_000038.5:c.3084T>G

NM_001127510.2:c.3084T>G

NM_001127511.2:c.3030T>G

NM_001354895.1:c.3084T>G

NM_001354896.1:c.3138T>G

NM_001354897.1:c.3114T>G

NM_001354898.1:c.3009T>G

NM_001354899.1:c.3000T>G

NM_001354900.1:c.2961T>G

NM_001354901.1:c.2907T>G

NM_001354902.1:c.2811T>G

NM_001354903.1:c.2781T>G

NM_001354904.1:c.2706T>G

NM_001354905.1:c.2604T>G

NM_001354906.1:c.2235T>G

NM_001127510.3:c.3084T>G

NM_001127511.3:c.3030T>G

NM_001354895.2:c.3084T>G

NM_001354896.2:c.3138T>G

NM_001354897.2:c.3114T>G

NM_001354898.2:c.3009T>G

NM_001354899.2:c.3000T>G

NM_001354900.2:c.2961T>G

NM_001354901.2:c.2907T>G

NM_001354902.2:c.2811T>G

NM_001354903.2:c.2781T>G

NM_001354904.2:c.2706T>G

NM_001354905.2:c.2604T>G

NM_001354906.2:c.2235T>G

Uncertain Significance

PS1_Moderate PM5_Supporting PM2_Supporting

PS4

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.3084T>G variant in APC is a missense variant predicted to cause the substitution of serine by arginine at codon 1028 (p.Ser1028Arg). Another missense variant c.3084T>A (p.Ser1028Arg) at the same nucleotide position leading to the same amino acid change has been classified as Likely Pathogenic for FAP according to the APC VCEP specifications (PS1_Moderate). Another missense variant c.3083G>T (p.Ser1028Ile) in the same codon leading to a different amino acid change has been classified as Likely Pathogenic for FAP according to the APC VCEP specifications (PM5_Supporting). This variant was identified in 1 proband with polyposis not meeting phenotype criteria (PS4_variable not met; Invitae internal data). Finally, this variant is absent from gnomAD v2.1.1 (PM2_Supporting). In Summary, due to insufficient evidence, this variant is a Variant of Uncertain Significance (VUS) for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: PS1_Moderate, PM2_Supporting, PM5_Supporting (VCEP specifications version 1; date of approval: 12/12/2022).

PS1_Moderate

The amino acid change (p.Ser1028Arg) resulting from a different nucleotide change c.3084T>A has been classified as Likely Pathogenic for FAP according to the APC-VCEP evidence codes (internal data Ambry and Invitae) (PS1_Moderate).

PM5_Supporting

Another missense variant NM_000038:c.3083G>T (p.Ser1028Ile) in the same codon has been classified as Likely Pathogenic for FAP according to the APC-VCEP evidence codes (internal data Ambry and Invitae) (PM5_Supporting).

PM2_Supporting

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

PS4

The variant NM_000038.6(APC):c.3084T>G (p.Ser1028Arg) was identified in 1 proband with polyposis not meeting phenotype criteria (not scored).

Curation History

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