Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • No CSPEC related information was provided by the message!
  • See Evidence submitted by expert panel for details.

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

CA10578350

233215 (ClinVar)

Gene: APC
Condition: familial adenomatous polyposis 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f412a530-ecd2-4ceb-bd23-0b0081fee028
Approved on: 2023-02-25
Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.3084T>A
NM_000038.6(APC):c.3084T>A (p.Ser1028Arg)
NC_000005.10:g.112838678T>A
CM000667.2:g.112838678T>A
NC_000005.9:g.112174375T>A
CM000667.1:g.112174375T>A
NC_000005.8:g.112202274T>A
NG_008481.4:g.151158T>A
ENST00000257430.9:c.3084T>A
ENST00000257430.8:c.3084T>A
ENST00000502371.2:n.1437T>A
ENST00000507379.5:c.3030T>A
ENST00000508376.6:c.3084T>A
ENST00000508624.5:c.*2406T>A
ENST00000512211.6:c.3084T>A
ENST00000520401.1:n.230+9706T>A
NM_000038.5:c.3084T>A
NM_001127510.2:c.3084T>A
NM_001127511.2:c.3030T>A
NM_001354895.1:c.3084T>A
NM_001354896.1:c.3138T>A
NM_001354897.1:c.3114T>A
NM_001354898.1:c.3009T>A
NM_001354899.1:c.3000T>A
NM_001354900.1:c.2961T>A
NM_001354901.1:c.2907T>A
NM_001354902.1:c.2811T>A
NM_001354903.1:c.2781T>A
NM_001354904.1:c.2706T>A
NM_001354905.1:c.2604T>A
NM_001354906.1:c.2235T>A
NM_001127510.3:c.3084T>A
NM_001127511.3:c.3030T>A
NM_001354895.2:c.3084T>A
NM_001354896.2:c.3138T>A
NM_001354897.2:c.3114T>A
NM_001354898.2:c.3009T>A
NM_001354899.2:c.3000T>A
NM_001354900.2:c.2961T>A
NM_001354901.2:c.2907T>A
NM_001354902.2:c.2811T>A
NM_001354903.2:c.2781T>A
NM_001354904.2:c.2706T>A
NM_001354905.2:c.2604T>A
NM_001354906.2:c.2235T>A
More

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"
Met criteria codes 5
PP1_Moderate PS3_Supporting PM5_Supporting PS4_Moderate PM2_Supporting
Not Met criteria codes 1
PS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP
The c.3084T>A variant in APC is a missense variant predicted to cause the substitution of serine by arginine at amino acid position 1028 p.(Ser1028Arg). This variant has been reported in 6 probands meeting phenotypic criteria, resulting in a total phenotype score of 3 (PS4_Moderate; Ambry Genetics internal data). This variant has been reported to segregate with FAP in 3 meioses in 2 families (6 meiosis in total) (PP1_Moderate; Ambry Genetics internal data). This variant is demonstrated to increased β-catenin regulated transcription activity and decreased binding to β-catenin by surface plasmon resonance (PS3_Supporting, Barcelona internal data). Another missense variant c.3083G>T (p.Ser1028Ile) in the same codon has been classified as Likely Pathogenic for FAP by the ClinGen InSiGHT Hereditary Colorectal Cancers/ Polyposis VCEP (PM5_Supporting). Finally, this variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant is classified as Likely Pathogenic for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: PS4_Moderate, PP1_Moderate, PS3_Supporting, PM2_Supporting, PM5_Supporting (VCEP Specification version 1; date of approval: 12/12/2022).
Met criteria codes
PP1_Moderate
This variant has been reported to segregate with FAP in 3 meioses in 2 families (6 meiosis in total) (PP1_moderate; Ambry Internal data).
PS3_Supporting
PS3_Supporting (increased β-catenin regulated transcription activity and decreased binding to β-catenin by surface plasmon resonance, internal data).
PM5_Supporting
Another missense variant c.3083G>T (p.Ser1028Ile) in the same codon has been classified as Likely Pathogenic for FAP by the ClinGen InSiGHT Hereditary Colorectal Cancers/ Polyposis VCEP.
PS4_Moderate
This variant has been reported in 6 probands meeting phenotypic criteria, resulting in a total phenotype score of 3 (PS4_Moderate, Ambry Genetics, Invitae internal data).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
Not Met criteria codes
PS1
The amino acid change (p.Ser1028Arg) resulting from a different nucleotide change c.3084T>G has been classified as a variant of unknown significance for FAP according to the APC-VCEP evidence codes (internal data Ambry and Invitae) (PS1_variable not met).
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.