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.1956C>T (p.His652=)

CA16618077

419202 (ClinVar)

Gene: APC
Condition: familial adenomatous polyposis 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 92b30bd7-d4e0-4d93-98c4-99e7e30f70c2
Approved on: 2023-02-25
Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.1956C>T
NM_000038.6(APC):c.1956C>T (p.His652=)
NC_000005.10:g.112835163C>T
CM000667.2:g.112835163C>T
NC_000005.9:g.112170860C>T
CM000667.1:g.112170860C>T
NC_000005.8:g.112198759C>T
NG_008481.4:g.147643C>T
ENST00000257430.9:c.1956C>T
ENST00000257430.8:c.1956C>T
ENST00000502371.2:n.309C>T
ENST00000504915.2:n.645C>T
ENST00000507379.5:c.1902C>T
ENST00000508376.6:c.1956C>T
ENST00000508624.5:c.*1278C>T
ENST00000512211.6:c.1956C>T
ENST00000520401.1:n.230+6191C>T
NM_000038.5:c.1956C>T
NM_001127510.2:c.1956C>T
NM_001127511.2:c.1902C>T
NM_001354895.1:c.1956C>T
NM_001354896.1:c.2010C>T
NM_001354897.1:c.1986C>T
NM_001354898.1:c.1881C>T
NM_001354899.1:c.1872C>T
NM_001354900.1:c.1833C>T
NM_001354901.1:c.1779C>T
NM_001354902.1:c.1683C>T
NM_001354903.1:c.1653C>T
NM_001354904.1:c.1578C>T
NM_001354905.1:c.1476C>T
NM_001354906.1:c.1107C>T
NM_001127510.3:c.1956C>T
NM_001127511.3:c.1902C>T
NM_001354895.2:c.1956C>T
NM_001354896.2:c.2010C>T
NM_001354897.2:c.1986C>T
NM_001354898.2:c.1881C>T
NM_001354899.2:c.1872C>T
NM_001354900.2:c.1833C>T
NM_001354901.2:c.1779C>T
NM_001354902.2:c.1683C>T
NM_001354903.2:c.1653C>T
NM_001354904.2:c.1578C>T
NM_001354905.2:c.1476C>T
NM_001354906.2:c.1107C>T
More

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"
Met criteria codes 3
PS3 PM2_Supporting PS4_Supporting

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.1956C>T variant in APC is predicted to be a synonymous (silent) variant (p.His652=). It is located at the third-last nucleotide of exon 15. Two RNA based RT-PCR assays demonstrate out-of-frame skipping of exon 15, with evidence that the variant allele produces <10% of the full-length transcript (PS3; PMID: 15459959, 22987206). This variant has been reported in 3 probands meeting least 1.5 phenotype points (PS4_Supporting; PMID: 15459959, 22987206). The variant is not reported in gnomAD (PM2_supporting). In summary, this variant meets the criteria to be 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: PS3, PS4_Supporting and PM2_Supporting (VCEP specifications version 1; date of approval: 12/12/2022).
Met criteria codes
PS3
PS3 according to the APC-VCEP modification of PS3: two RNA based RT-PCR assays demonstrate out-of-frame skipping of exon 15, with evidence that the variant allele produces < 10% of the full-length transcript.
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
PS4_Supporting
1,5 phenotype points (PS4_Supporting): PMID: 15459959: index and father with ≥ 20 colorectal adenomas a with 20 to 70 yr PMID: 22987206: index with ≥ 20 colorectal adenomas a with 20 to 70 yr, mother affected CRC but no phenotypic information
Curation History
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