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]
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Variant: NM_000038.6(APC):c.4906G>T (p.Asp1636Tyr)

CA009798

183069 (ClinVar)

Gene: APC
Condition: familial adenomatous polyposis 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 2850fdca-2c61-433f-a353-63c5996acc33
Approved on: 2023-02-26
Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.4906G>T
NM_000038.6(APC):c.4906G>T (p.Asp1636Tyr)
NC_000005.10:g.112840500G>T
CM000667.2:g.112840500G>T
NC_000005.9:g.112176197G>T
CM000667.1:g.112176197G>T
NC_000005.8:g.112204096G>T
NG_008481.4:g.152980G>T
ENST00000257430.9:c.4906G>T
ENST00000257430.8:c.4906G>T
ENST00000508376.6:c.4906G>T
ENST00000508624.5:c.*4228G>T
ENST00000520401.1:n.230+11528G>T
NM_000038.5:c.4906G>T
NM_001127510.2:c.4906G>T
NM_001127511.2:c.4852G>T
NM_001354895.1:c.4906G>T
NM_001354896.1:c.4960G>T
NM_001354897.1:c.4936G>T
NM_001354898.1:c.4831G>T
NM_001354899.1:c.4822G>T
NM_001354900.1:c.4783G>T
NM_001354901.1:c.4729G>T
NM_001354902.1:c.4633G>T
NM_001354903.1:c.4603G>T
NM_001354904.1:c.4528G>T
NM_001354905.1:c.4426G>T
NM_001354906.1:c.4057G>T
NM_001127510.3:c.4906G>T
NM_001127511.3:c.4852G>T
NM_001354895.2:c.4906G>T
NM_001354896.2:c.4960G>T
NM_001354897.2:c.4936G>T
NM_001354898.2:c.4831G>T
NM_001354899.2:c.4822G>T
NM_001354900.2:c.4783G>T
NM_001354901.2:c.4729G>T
NM_001354902.2:c.4633G>T
NM_001354903.2:c.4603G>T
NM_001354904.2:c.4528G>T
NM_001354905.2:c.4426G>T
NM_001354906.2:c.4057G>T

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"
Met criteria codes 4
PM2_Supporting BS2 BP1 BP2
Not Met criteria codes 1
BP4

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.4906G>T variant in APC is a missense variant predicted to cause the substitution of aspartate by tyrosine at amino acid position 1636 (p.Asp1636Tyr). APC is defined by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (HCCP VCEP) as a gene for which primarily truncating variants are known to cause disease (BP1). This variant has been observed in trans with the variant c.3100G>T (p.Glu1034*) (Bonn internal data) which is classified as Pathogenic by the HCCP VCEP in an individual with FAP (BP2). This variant has been observed in heterozygous state in 11 unrelated healthy adult individuals worth ≥ 10 healthy individual points in total (BS2; Ambry Genetics internal data). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, although there are both pathogenic and benign types of evidence for this variant, the pathogenic/benign evidence is not considered inconsistent with the final Likely Benign classification for FAP. ACMG/AMP criteria applied, as specified by the HCCP VCEP: BS2, BP1, and BP2 (VCEP specifications version 1; date of approval: 12/12/2022).
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
BS2
This variant has been observed in heterozygous state in 11 healthy unrelated adult individuals worth ≥ 10 healthy individual points in total (BS2; Ambry Genetics).
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 (BP1).
BP2
This variant has been observed in trans with the variant c.3100G>T, p.Glu1034Ter (internal data, Institute of Human Genetics, Bonn, Germany) which is classified as pathogenic by the ClinGen InSiGHT Hereditary Colorectal Cancer/ Polyposis VCEP in an individual with FAP. (BP2)
Not Met criteria codes
BP4
N/A for missense variants
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