The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: APC vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000038.6(APC):c.835-7T>G

CA645372415

433614 (ClinVar)

Gene: APC
Condition: familial adenomatous polyposis 1
Inheritance Mode: Autosomal dominant inheritance
UUID: 25453e5d-e593-49aa-b0b2-66bb5fdf0e0c
Approved on: 2025-05-15
Published on: 2025-05-19

HGVS expressions

NM_000038.6:c.835-7T>G
NM_000038.6(APC):c.835-7T>G
NC_000005.10:g.112815488T>G
CM000667.2:g.112815488T>G
NC_000005.9:g.112151185T>G
CM000667.1:g.112151185T>G
NC_000005.8:g.112179084T>G
NG_008481.4:g.127968T>G
ENST00000502371.3:c.835-7T>G
ENST00000504915.3:c.835-7T>G
ENST00000505084.2:n.891-7T>G
ENST00000505350.2:c.*841-7T>G
ENST00000507379.6:c.781-7T>G
ENST00000509732.6:c.835-7T>G
ENST00000512211.7:c.835-7T>G
ENST00000257430.9:c.835-7T>G
ENST00000257430.8:c.835-7T>G
ENST00000507379.5:c.781-7T>G
ENST00000508376.6:c.835-7T>G
ENST00000508624.5:c.*157-7T>G
ENST00000512211.6:c.835-7T>G
NM_000038.5:c.835-7T>G
NM_001127510.2:c.835-7T>G
NM_001127511.2:c.781-7T>G
NM_001354895.1:c.835-7T>G
NM_001354896.1:c.835-7T>G
NM_001354897.1:c.865-7T>G
NM_001354898.1:c.760-7T>G
NM_001354899.1:c.751-7T>G
NM_001354900.1:c.658-7T>G
NM_001354901.1:c.658-7T>G
NM_001354902.1:c.865-7T>G
NM_001354903.1:c.835-7T>G
NM_001354904.1:c.760-7T>G
NM_001354905.1:c.658-7T>G
NM_001354906.1:c.-15-7T>G
NM_001127510.3:c.835-7T>G
NM_001127511.3:c.781-7T>G
NM_001354895.2:c.835-7T>G
NM_001354896.2:c.835-7T>G
NM_001354897.2:c.865-7T>G
NM_001354898.2:c.760-7T>G
NM_001354899.2:c.751-7T>G
NM_001354900.2:c.658-7T>G
NM_001354901.2:c.658-7T>G
NM_001354902.2:c.865-7T>G
NM_001354903.2:c.835-7T>G
NM_001354904.2:c.760-7T>G
NM_001354905.2:c.658-7T>G
NM_001354906.2:c.-15-7T>G
More

Likely Pathogenic

Met criteria codes 4
PS3_Moderate PP3 PM2 PS4_Moderate

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for APC Version 2.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP
The NM_000038.6(APC):c.835-7T>G variant in APC is an intronic variant in intron 8. This variant has been reported in 3 families meeting phenotypic criteria, resulting in a total phenotype score of 2.5 (PS4_Moderate, PMID: 18433509, internal data Labcorp Genetics (formerly Invitae)). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The results from ≥ 2 in silico splicing predictors (SpliceAI and MaxEnt) indicate that this variant may affect splicing by disrupting the acceptor splice site of intron 8 and creating a cryptic acceptor splice site (PP3). RT-PCR sequencing of cDNA demonstrated that the variant impacts splicing by insertion of the last six bases of intron 8 between exon 8 and 9, the second inserted codon is a stop codon. However, relative quantitation of full-length normal transcript versus mutant was not performed (PS3_Moderate, PMID 18433509). In summary, this variant is a Likely Pathogenic variant for autosomal-dominant inherited FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP: PS4_Moderate, PS3_Moderate, PM2_Supporting and PP3 applied (VCEP specifications version v2.1.0; date of approval 11/24/2023).
Met criteria codes
PS3_Moderate
RT-PCR sequencing of cDNA demonstrated that the variant impacts splicing by insertion of the last six bases of intron 8 between exon 8 and 9, the second inserted codon is a stop codon. However, relative quantitation of full-length normal transcript versus mutant was not performed (PS3_Moderate, PMID 18433509).
PP3
The results from ≥ 2 in silico splicing predictors (SpliceAI and MaxEnt) indicate that this variant may affect splicing by disrupting the acceptor splice site of intron 8 and creating a cryptic acceptor splice site (PP3).
PM2
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
PS4_Moderate
This variant has been reported in 3 families meeting phenotypic criteria, resulting in a total phenotype score of 2.5 (PS4_Moderate, PMID: 18433509, internal data Labcorp Genetics (formerly Invitae)).
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.