ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6857C>T (p.Ala2286Val) (rs200587641)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000120028 SCV000149025 likely benign not specified 2017-12-15 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 RCV000122796 SCV000166053 benign Familial adenomatous polyposis 1 2020-12-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000115116 SCV000183908 likely benign Hereditary cancer-predisposing syndrome 2018-09-20 criteria provided, single submitter clinical testing Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign);Other data supporting benign classification
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587401 SCV000694101 likely benign not provided 2017-01-19 criteria provided, single submitter clinical testing Variant summary: The APC c.6857C>T (p.Ala2286Val) variant involves the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 31/121008 control chromosomes (1 homozygote) at a frequency of 0.0002562, which is approximately 4 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this variant is likely a benign polymorphism. This variant has been reported in one individual who also carries a potenially pathogenic APC variant (c.896_897delCT/p.Ser299CysfsX27, UMD database). In addition, at least one clinical diagnostics laboratory classified this variant as likely benign. Taken together, this variant is classified as likely benign.
Counsyl RCV000122796 SCV000786262 uncertain significance Familial adenomatous polyposis 1 2018-03-27 criteria provided, single submitter clinical testing
GeneKor MSA RCV000115116 SCV000821823 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Mendelics RCV000122796 SCV000838144 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Color Health, Inc RCV000115116 SCV000910682 likely benign Hereditary cancer-predisposing syndrome 2016-03-21 criteria provided, single submitter clinical testing
ITMI RCV000120028 SCV000084159 not provided not specified 2013-09-19 no assertion provided reference population
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000501432 SCV000591203 likely benign Familial colorectal cancer no assertion criteria provided clinical testing The APC __p.Ala2286Val variant was identified in dbSNP (ID: rs200587641). This variant is reported in ClinVar (Classified as LB by GeneDx, Ambry, Integrated Genetics, Color. Classified as B by Invitae. Classified as VUS by Counsyl, GeneKorMSA, Mendelics. Classified as P by COGR). The variant was identified in control databases in 61 of 250898 chromosomes (0 homozygous) at a frequency of 0.0002232 and was observed at the highest frequency in the Latino population in 29 of 35374 chromosomes (freq: 0.0008198) (Genome Aggregation Database March 6, 2019, v2.1.1). This variant has been reported in one individual who also carries a potenially pathogenic APC variant (c.896_897delCT/p.Ser299Cysfs*27, UMD database). The p.Ala2286 residue is not conserved in mammals, and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity.The variant occurs outside of the splicing consensus sequence and 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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