ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6609T>C (p.Val2203=) (rs149328018)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000987579 SCV000166050 benign Familial adenomatous polyposis 1 2020-12-08 criteria provided, single submitter clinical testing
GeneDx RCV000211926 SCV000209480 benign not specified 2014-08-08 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.
Ambry Genetics RCV000159523 SCV000214020 likely benign Hereditary cancer-predisposing syndrome 2014-11-06 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.
Illumina Clinical Services Laboratory,Illumina RCV000399599 SCV000452039 likely benign APC-Associated Polyposis Disorders 2018-01-12 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000211926 SCV000600132 likely benign not specified 2017-03-04 criteria provided, single submitter clinical testing
Color Health, Inc RCV000159523 SCV000681810 likely benign Hereditary cancer-predisposing syndrome 2016-05-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589578 SCV000694099 benign not provided 2016-03-07 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589578 SCV000887542 likely benign not provided 2017-03-04 criteria provided, single submitter clinical testing
Mendelics RCV000987579 SCV001136935 likely benign Familial adenomatous polyposis 1 2019-05-28 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000159523 SCV000693486 likely benign Hereditary cancer-predisposing syndrome 2017-06-27 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356436 SCV001551602 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The APC p.Val2203= variant was identified in the literature, however, the frequency of this variant in an affected population was not provided. The variant was also identified in ClinVar (3x as Benign by GeneDx, Invitae and Integrated Genetics, 5x as Likely Benign, and 1x as Uncertain). The variant was not identified in LOVD 3.0 or UMD-LSDB. The variant was identified in control databases in 79 of 276074 chromosomes at a frequency of 0.00023, increasing the likelihood that this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 23952 chromosomes (freq: 0.00004), Latino in 1 of 34370 chromosomes (freq: 0.00003), European Non-Finnish in 12 of 125826 chromosomes (freq: 0.0001), and Ashkenazi Jewish in 65 of 10124 chromosomes (freq: 0.006). The variant was not observed in the Other, East Asian, Finnish, or South Asian populations. The p.Val2203= 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. In addition, the variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as likely benign.

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