ClinVar Miner

Submissions for variant NM_000038.6(APC):c.388A>G (p.Ser130Gly) (rs150973053)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000034387 SCV000166032 benign not provided 2019-03-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129715 SCV000184518 likely benign Hereditary cancer-predisposing syndrome 2017-07-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Subpopulation frequency in support of benign classification,Other data supporting benign classification
GeneDx RCV000211891 SCV000209564 likely benign not specified 2017-10-23 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000034387 SCV000694040 likely benign not provided 2017-04-27 criteria provided, single submitter clinical testing Variant summary: The APC c.388A>G (p.Ser130Gly) variant involves the alteration of a conserved nucleotide, resulting in a missense substitution in the adenomatous polyposis coli protein domain (InterPro). 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). 3/5 splice prediction tools predict a gain of a cryptic splicing donor site. ESE finder predicts that this variant does not significantly affect ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC and in control cohorts from the literature in 26 of 123278 control chromosomes from all ethnicities, but was predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.000375 (25/66728 chromosomes). This frequency is about 5 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), providing strong evidence that this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. Variant was observed in FAP and CRC patients however without strong evidence for pathogenicity. Moreover, in one patient, it was found to co-occurre with a potentially pathogenic APC variant p.Ser1272X indicating a non-contributory role of the variant to the disease in this patient (Rosa__Human_Mutation_2004). Clinical laboratories classify variant as Likely Benign/Uncertain via ClinVar (without evidence to independently evaluate). Taken together, this variant is classified as likely benign.
Mendelics RCV000122775 SCV000838062 likely benign Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000129715 SCV000902599 likely benign Hereditary cancer-predisposing syndrome 2016-03-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000034387 SCV001133330 benign not provided 2019-02-13 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034387 SCV000043104 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
CSER _CC_NCGL, University of Washington RCV000417265 SCV000503532 uncertain significance Familial adenomatous polyposis 2016-08-01 no assertion criteria provided research Found in patient having exome sequencing due to suspicion for hereditary colon cancer and/or polyps. Patient is a 40 year old with a history of colon cancer diagnosed at age 39 and a family history of colon polyps.

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