ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3352A>G (p.Asn1118Asp) (rs140493115)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000034411 SCV000166028 benign not provided 2019-03-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129162 SCV000183894 benign Hereditary cancer-predisposing syndrome 2014-12-09 criteria provided, single submitter clinical testing
GeneDx RCV000200963 SCV000209513 likely benign not specified 2017-12-06 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.
Color RCV000129162 SCV000681593 likely benign Hereditary cancer-predisposing syndrome 2016-03-18 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000200963 SCV000862006 likely benign not specified 2018-06-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000034411 SCV000887521 benign not provided 2018-04-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000200963 SCV000916477 benign not specified 2017-10-06 criteria provided, single submitter clinical testing Variant summary: The APC c.3352A>G (p.Asn1118Asp) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 110/278362 control chromosomes, predominantly observed in the Ashkenazi Jewish subpopulation at a frequency of 0.009593 (97/10112). This frequency is about 134 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this is likely a benign polymorphism found primarily in the populations of Ashkenazi Jewish origin. This variant has been reported in multiple affected individuals and two families with evidence of lack of co-segregation of variant with disease (Nagase_1992 and Zhou_2004). Moreover, one colon cancer patient also carried a pathogenic BRCA2 variant c.5946del/p.S1982RfsX22 (Pearlman_2016), further supporting the benign nature of this variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign; one other lab classified it as VUS, all without evidence for independent evaluation. Taken together, especially considering the high MAF in controls, evidence of lack of co-segregation of variant with disease, and co-occurrence with another pathogenic variant, this variant is classified as benign.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034411 SCV000043120 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000200963 SCV000691734 uncertain significance not specified no assertion criteria provided clinical testing
True Health Diagnostics RCV000129162 SCV000693476 likely benign Hereditary cancer-predisposing syndrome 2017-09-28 no assertion criteria provided clinical testing

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