Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000038.6(APC):c.7862C>G (p.Ser2621Cys)

CA014123

41516 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: cc19eee0-403e-47f1-acab-77bd1720f3ed

Approved on: 2023-02-26

Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.7862C>G

NM_000038.6(APC):c.7862C>G (p.Ser2621Cys)

NC_000005.10:g.112843456C>G

CM000667.2:g.112843456C>G

NC_000005.9:g.112179153C>G

CM000667.1:g.112179153C>G

NC_000005.8:g.112207052C>G

NG_008481.4:g.155936C>G

ENST00000257430.9:c.7862C>G

ENST00000257430.8:c.7862C>G

ENST00000508376.6:c.7862C>G

ENST00000520401.1:n.231-13193C>G

NM_000038.5:c.7862C>G

NM_001127510.2:c.7862C>G

NM_001127511.2:c.7808C>G

NM_001354895.1:c.7862C>G

NM_001354896.1:c.7916C>G

NM_001354897.1:c.7892C>G

NM_001354898.1:c.7787C>G

NM_001354899.1:c.7778C>G

NM_001354900.1:c.7739C>G

NM_001354901.1:c.7685C>G

NM_001354902.1:c.7589C>G

NM_001354903.1:c.7559C>G

NM_001354904.1:c.7484C>G

NM_001354905.1:c.7382C>G

NM_001354906.1:c.7013C>G

NM_001127510.3:c.7862C>G

NM_001127511.3:c.7808C>G

NM_001354895.2:c.7862C>G

NM_001354896.2:c.7916C>G

NM_001354897.2:c.7892C>G

NM_001354898.2:c.7787C>G

NM_001354899.2:c.7778C>G

NM_001354900.2:c.7739C>G

NM_001354901.2:c.7685C>G

NM_001354902.2:c.7589C>G

NM_001354903.2:c.7559C>G

NM_001354904.2:c.7484C>G

NM_001354905.2:c.7382C>G

NM_001354906.2:c.7013C>G

Benign

BA1 BS2 BP1

Evidence Links 0

Expert Panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

The c.7862C>G variant in APC is a missense variant predicted to cause the substitution of Serine by Cysteine at amino acid position 2621 (p.Ser2621Cys). This variant has been observed in more than 10 heterozygous individuals over the age of 50 with no features of FAP, worth more than 10 healthy individual points (BS2; Ambry internal data). APC is defined by the ClinGen APC VCEP as a gene for which primarily truncating variants are known to cause disease (BP1). The highest population minor allele frequency in the non-cancer cohort of gnomAD v2.1.1 is 0.5021% in the non-Finnish European population, which is higher than the ClinGen APC VCEP threshold of 0.1% for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as Benign for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: BA1, BS2, and BP1 (VCEP specifications version 1; date of approval: 12/12/2022).

BA1

The highest population minor allele frequency in the non-cancer cohort of gnomAD v2.1.1 is 0.5021% in the non-Finnish European population, which is higher than the ClinGen APC VCEP threshold of 0.1% for BA1, and therefore meets this criterion (BA1).

BS2

This variant has been observed in more than 10 heterozygous individuals over the age of 50 with no features of FAP (Ambry internal data).

BP1

APC, in which the variant was identified, is defined by the ClinGen APC VCEP as a gene for which primarily truncating variants are known to cause disease (BP1).

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