ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2205G>A (p.Ala735=) (rs141001261)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162793 SCV000213271 likely benign Hereditary cancer-predisposing syndrome 2014-12-19 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.
Invitae RCV000199939 SCV000252908 likely benign Familial adenomatous polyposis 1 2020-11-25 criteria provided, single submitter clinical testing
Counsyl RCV000199939 SCV000488961 likely benign Familial adenomatous polyposis 1 2016-07-26 criteria provided, single submitter clinical testing
GeneDx RCV000429527 SCV000512067 benign not specified 2015-03-20 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000429527 SCV000600058 benign not specified 2017-07-13 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162793 SCV000681507 likely benign Hereditary cancer-predisposing syndrome 2016-05-19 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587002 SCV000694009 benign not provided 2016-06-10 criteria provided, single submitter clinical testing Variant summary: The APC c.2205G>A (p.Ala735Ala) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 in silico prediction tools predicting no significant effect on splicing, although these predictions have yet to be functionally assessed. This variant was observed in the large, broad control population, ExAC, with an allele frequency of 16/120502 (1/7530), predominantly observed in the African subpopulation, 5/10246 (1/2049), which exceeds the estimated maximal expected allele frequency for a pathogenic APC variant of 1/14005 (0.0000714). Therefore, suggesting this is likely a benign polymorphism found primarily in population(s)of African origin. In addition, multiple clinical diagnostic laboratories and a publication classified this variant as Likely Benign. Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587002 SCV000887508 benign not provided 2017-07-13 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000587002 SCV001249415 likely benign not provided 2019-10-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001155353 SCV001316777 uncertain significance APC-Associated Polyposis Disorders 2018-07-10 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353912 SCV000591109 likely benign Carcinoma of colon no assertion criteria provided clinical testing The p.Ala735Ala variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant was not identified in the literature, but was identified in dbSNP (ID: rs141001261) and in the COSMIC database. The variant is listed in the NHLBI Exome Sequencing Project with frequencies of 0.0001 in European American alleles and 0.0002 in African American alleles, though these frequencies are based solely on one occurrence of the variant allele in each cohort. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as predicted benign.

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