ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6387G>A (p.Ser2129=) (rs374310157)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163062 SCV000213556 likely benign Hereditary cancer-predisposing syndrome 2014-12-09 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 RCV001083836 SCV000252591 benign Familial adenomatous polyposis 1 2020-12-04 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000293113 SCV000452034 likely benign APC-Associated Polyposis Disorders 2016-06-14 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508036 SCV000600124 benign not specified 2020-01-20 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163062 SCV000681797 benign Hereditary cancer-predisposing syndrome 2016-05-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589653 SCV000694091 benign not provided 2017-01-26 criteria provided, single submitter clinical testing Variant summary: The APC c.6387G>A (p.Ser2129Ser) variant causes a synonymous change involving a non-conserved nucleotide, 4/5 splice prediction tools predict no significant impact on normal splicing, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 34/121086 (1/3561), predominantly in the Latino cohort, 30/11544 (1/384), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic APC variant of 1/14005. Therefore, suggesting this is likely a benign polymorphism found primarily in population(s) of Latino origin. The variant of interest has not been, to our knowledge, reported in affected individuals via publications, although multiple clinical diagnostic laboratories cite the variant with a classification of "likely benign/benign." Therefore, the variant of interest has been classified as Benign.
GeneDx RCV000589653 SCV001838322 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355704 SCV001550660 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The APC p.Ser2129= variant was not identified in the literature nor was it identified in the COGR, Cosmic, LOVD 3.0, UMD-LSDB, or in Zhejiang University databases. The variant was identified in dbSNP (ID: rs374310157) as "With other allele ", and in ClinVar (classified as benign by Invitae, Color Genomics, Integrated Genetics/Laboratory Corporation of America; as likely benign by Ambry Genetics, and one clinical laboratory), databases. The variant was identified in control databases in 80 of 276588 chromosomes at a frequency of 0.0003 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 1 of 6450 chromosomes (freq: 0.00015), Latino in 72 of 34390 chromosomes (freq: 0.002), European in 6 of 126234 chromosomes (freq: 0.000048), and South Asian in 1 of 30774 chromosomes (freq: 0.00003); it was not observed in the African, Ashkenazi Jewish, East Asian, and in Finnish populations. The p.Ser2129= 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, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. 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 likely benign.

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