Submissions for variant NM_000038.6(APC):c.7888G>A (p.Val2630Ile)

gnomAD frequency: 0.00006  dbSNP: rs199688874

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000034402	SCV000149033	likely benign	not provided	2021-04-26	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28502729, 22703879)
Ambry Genetics	RCV000115124	SCV000184471	likely benign	Hereditary cancer-predisposing syndrome	2018-05-23	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl	RCV000409244	SCV000488215	uncertain significance	Familial adenomatous polyposis 1	2016-01-27	criteria provided, single submitter	clinical testing
Invitae	RCV003534319	SCV000552684	likely benign	Familial adenomatous polyposis 1	2024-01-26	criteria provided, single submitter	clinical testing
Mendelics	RCV000409244	SCV000838157	uncertain significance	Familial adenomatous polyposis 1	2018-07-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000115124	SCV000910742	likely benign	Hereditary cancer-predisposing syndrome	2018-04-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000254630	SCV000918437	likely benign	not specified	2022-08-18	criteria provided, single submitter	clinical testing	Variant summary: APC c.7888G>A (p.Val2630Ile) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.6e-05 in 250304 control chromosomes, predominantly at a frequency of 0.00019 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in APC causing Familial Adenomatous Polyposis phenotype (7.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.7888G>A has been reported in the literature in a validation study (Rey_2017). This report does not provide unequivocal conclusions about association of the variant with Familial Adenomatous Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven ClinVar submitters (evaluation after 2014) cite the variant as likely benign (n=5) and as uncertain significance (n=2). Based on the evidence outlined above, the variant was classified as likely benign.
Sema4, Sema4	RCV000115124	SCV002530922	likely benign	Hereditary cancer-predisposing syndrome	2021-04-19	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000409244	SCV004018833	likely benign	Familial adenomatous polyposis 1	2023-02-23	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant has been observed in conjunction with multiple pathogenic variants, reducing the likelihood this variant itself is pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000034402	SCV004159232	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	APC: BP4
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034402	SCV000043144	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000034402	SCV001957561	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000034402	SCV001966140	likely benign	not provided		no assertion criteria provided	clinical testing