ClinVar Miner

Submissions for variant NM_000038.6(APC):c.757G>A (p.Gly253Ser)

gnomAD frequency: 0.00003  dbSNP: rs772806807
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003316239 SCV000282827 likely benign Familial adenomatous polyposis 1 2024-01-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV000562662 SCV000667227 likely benign Hereditary cancer-predisposing syndrome 2021-01-26 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 RCV000229496 SCV000785247 uncertain significance Familial adenomatous polyposis 1 2017-06-19 criteria provided, single submitter clinical testing
Mendelics RCV000229496 SCV000838068 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000562662 SCV000902854 benign Hereditary cancer-predisposing syndrome 2016-06-15 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001156936 SCV001318476 uncertain significance APC-Associated Polyposis Disorders 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193538 SCV001362437 uncertain significance not specified 2019-01-25 criteria provided, single submitter clinical testing Variant summary: APC c.757G>A (p.Gly253Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.3e-05 in 276640 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.757G>A has been reported in the literature in cancer samples and individuals affected with cancer, specifically T cell acute lymphoblastic leukemia, familial gastrointestinal polyposis/cancers and pancreatic ductal adenocarcinoma (Kohda_2016, Ohmoto_2016, Kalender_2012). These reports do 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. Five ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV001193538 SCV002760344 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003316239 SCV004019656 uncertain significance Familial adenomatous polyposis 1 2023-02-15 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV000229496 SCV004198303 uncertain significance Familial adenomatous polyposis 1 2023-09-19 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003477779 SCV004220587 likely benign not provided 2018-12-18 criteria provided, single submitter clinical testing
3DMed Clinical Laboratory Inc RCV000677749 SCV000803905 uncertain significance Colon cancer 2017-06-14 no assertion criteria provided clinical testing
GenomeConnect, ClinGen RCV001156936 SCV002075117 not provided APC-Associated Polyposis Disorders no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 04-28-2021 by Lab or GTR ID 320353. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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