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]
  • 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.70C>T (p.Arg24Ter)

CA012843

184702 (ClinVar)

Gene: APC
Condition: familial adenomatous polyposis 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 2648e21f-e671-42e2-b3ec-67e364423e2c
Approved on: 2025-05-15
Published on: 2025-05-19

HGVS expressions

NM_000038.6:c.70C>T
NM_000038.6(APC):c.70C>T (p.Arg24Ter)
NC_000005.10:g.112754960C>T
CM000667.2:g.112754960C>T
NC_000005.9:g.112090657C>T
CM000667.1:g.112090657C>T
NC_000005.8:g.112118556C>T
NG_008481.4:g.67440C>T
ENST00000502371.3:c.70C>T
ENST00000504915.3:c.70C>T
ENST00000505084.2:n.126C>T
ENST00000505350.2:c.*76C>T
ENST00000507379.6:c.166-11366C>T
ENST00000509732.6:c.70C>T
ENST00000512211.7:c.70C>T
ENST00000257430.9:c.70C>T
ENST00000257430.8:c.70C>T
ENST00000505350.1:c.*76C>T
ENST00000507379.5:c.166-11366C>T
ENST00000508376.6:c.70C>T
ENST00000508624.5:c.70C>T
ENST00000509732.5:c.70C>T
ENST00000512211.6:c.70C>T
NM_000038.5:c.70C>T
NM_001127510.2:c.70C>T
NM_001127511.2:c.166-11366C>T
NM_001354895.1:c.70C>T
NM_001354896.1:c.70C>T
NM_001354897.1:c.166-11366C>T
NM_001354898.1:c.61-11366C>T
NM_001354899.1:c.70C>T
NM_001354900.1:c.-42-11366C>T
NM_001354901.1:c.-42-11366C>T
NM_001354902.1:c.166-11366C>T
NM_001354903.1:c.70C>T
NM_001354904.1:c.61-11366C>T
NM_001354905.1:c.-42-11366C>T
NM_001354906.1:c.-966C>T
NM_001127510.3:c.70C>T
NM_001127511.3:c.166-11366C>T
NM_001354895.2:c.70C>T
NM_001354896.2:c.70C>T
NM_001354897.2:c.166-11366C>T
NM_001354898.2:c.61-11366C>T
NM_001354899.2:c.70C>T
NM_001354900.2:c.-42-11366C>T
NM_001354901.2:c.-42-11366C>T
NM_001354902.2:c.166-11366C>T
NM_001354903.2:c.70C>T
NM_001354904.2:c.61-11366C>T
NM_001354905.2:c.-42-11366C>T
NM_001354906.2:c.-966C>T
More

Uncertain Significance

Met criteria codes 2
PS4_Supporting BS2
Not Met criteria codes 4
PM2 PVS1 BA1 BS1

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.70C>T (p.Arg24Ter) in APC is a nonsense variant located 5’ of codon 49, thus PVS1 is not applicable based on the ACMG/AMP criteria specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP (HCCP VCEP). The total minor allele frequency in gnomAD v2.1.1 (non-cancer) is 0.00002 (6/268,098 alleles), however, no value is given for the “filtering allele frequency” (FAF) (PM2_Supporting and BS1 not met). This variant has been observed in heterozygous state in 67 individuals, which are reported either with a very mild polyposis phenotype (only 3 carriers fulfilled 0.5 phenotype points each; PS4_Supporting) or without a colorectal cancer/polyposis associated phenotype (at least 10 healthy unrelated adult individuals worth ≥ 10 healthy individual points in total; BS2) (PMID: 28135145 and 18433509, internal data Ambry Genetics, GeneDX and Labcorp Genetics (formerly Invitae)). Due to conflicting evidence, this variant is classified as a variant of uncertain significance for autosomal-dominant inherited FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: criterion PS4_Supporting and BS2 applied (VCEP specifications version v2.1.0; date of approval 11/24/2023).
Met criteria codes
PS4_Supporting
This variant has been observed in heterozygous state in 67 individuals, which are reported either with a very mild polyposis phenotype (only 3 carriers fulfilled 0.5 phenotype points each; PS4_Supporting) or without a colorectal cancer/polyposis associated phenotype (at least 10 healthy unrelated adult individuals worth ≥ 10 healthy individual points in total; BS2) (PMID: 28135145 and 18433509, internal data Ambry Genetics, GeneDX and Labcorp Genetics (formerly Invitae)).
BS2
This variant has been observed in heterozygous state in 67 individuals, which are reported either with a very mild polyposis phenotype (only 3 carriers fulfilled 0.5 phenotype points each; PS4_Supporting) or without a colorectal cancer/polyposis associated phenotype (at least 10 healthy unrelated adult individuals worth ≥ 10 healthy individual points in total; BS2) (PMID: 28135145 and 18433509, internal data Ambry Genetics, GeneDX and Labcorp Genetics (formerly Invitae)).
Not Met criteria codes
PM2
The total minor allele frequency in gnomAD v2.1.1 (non-cancer) is 0.00002 (6/268,098 alleles), however, no value is given for the “filtering allele frequency” (FAF) (PM2_Supporting not met).
PVS1
The NM_000038.6(APC):c.70C>T (p.Arg24Ter) in APC is a nonsense variant located 5’ of codon 49, thus PVS1 is not applicable based on the ACMG/AMP criteria specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP (HCCP VCEP).
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
The total minor allele frequency in gnomAD v2.1.1 (non-cancer) is 0.00002 (6/268,098 alleles), however, no value is given for the “filtering allele frequency” (FAF) (BS1 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.