ClinVar Miner

Submissions for variant NM_000038.6(APC):c.8068G>A (p.Ala2690Thr) (rs140868933)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000200966 SCV000149034 benign not specified 2018-01-30 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.
Invitae RCV000122806 SCV000166063 benign Familial adenomatous polyposis 1 2020-12-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000115125 SCV000183836 benign Hereditary cancer-predisposing syndrome 2014-12-30 criteria provided, single submitter clinical testing Does not segregate with disease in family study (genes with incomplete penetrance);General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;In silico models in agreement (benign)
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000200966 SCV000538290 benign not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 1.5% (102/6614) Finnish; ClinVar: 3 B, 1 VUS
Color Health, Inc RCV000115125 SCV000681909 benign Hereditary cancer-predisposing syndrome 2016-03-22 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000200966 SCV000805476 benign not specified 2017-10-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759448 SCV000888774 benign not provided 2016-03-25 criteria provided, single submitter clinical testing
Pathway Genomics RCV000122806 SCV000207331 benign Familial adenomatous polyposis 1 2014-11-06 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353775 SCV000591219 likely benign Carcinoma of colon no assertion criteria provided clinical testing The APC p.Ala2690Thr variant was not identified in the literature. The variant was identified in dbSNP (rs140868933) as “with other allele”, ClinVar (classified as benign by Invitae, Ambry Genetics, GeneDx, Color and 4 other submitters and likely benign by True Health Diagnostics and 1 other submitter), LOVD 3.0 (observed 6x) and UMD-LSDB (observed 2x). The variant was identified in control databases in 663 of 282,646 chromosomes (3 homozygous) at a frequency of 0.002 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: Finnish in 354 of 25,120 chromosomes (freq: 0.01), Other in 18 of 7220 chromosomes (freq: 0.002), European in 264 of 128,976 chromosomes (freq: 0.002), South Asian in 19 of 30,616 chromosomes (freq: 0.0006), Latino in 6 of 35,434 chromosomes (freq: 0.0002), African in 2 of 24,962 chromosomes (freq: 0.00008), while the variant was not observed in the Ashkenazi Jewish, and East Asian populations. The p.Ala2690Thr residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
True Health Diagnostics RCV000115125 SCV000805209 likely benign Hereditary cancer-predisposing syndrome 2018-04-05 no assertion criteria provided clinical testing

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