ClinVar Miner

Submissions for variant NM_005188.4(CBL):c.2542G>A (p.Ala848Thr)

gnomAD frequency: 0.00010  dbSNP: rs141710973
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000033373 SCV000057278 likely benign not specified 2012-08-20 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.
PreventionGenetics, part of Exact Sciences RCV000033373 SCV000310874 likely benign not specified criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000475436 SCV000555933 likely benign RASopathy 2023-12-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000033373 SCV001361042 likely benign not specified 2019-12-24 criteria provided, single submitter clinical testing Variant summary: CBL c.2542G>A (p.Ala848Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00015 in 251470 control chromosomes. The observed variant frequency is approximately 60 fold of the estimated maximal expected allele frequency for a pathogenic variant in CBL causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is benign. c.2542G>A has been reported in the literature in a study examining the prevalence of germline mutations in pediatric cancer where it was classified with a panel decision of probably benign (Zhang_2015). This report does not provide unequivocal conclusions about association of the variant with Noonan Syndrome and Related Conditions. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Genetic Services Laboratory, University of Chicago RCV000033373 SCV002070074 likely benign not specified 2020-12-03 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV003421940 SCV004129488 likely benign not provided 2023-09-01 criteria provided, single submitter clinical testing CBL: BP4, BS1
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV003421940 SCV004563233 likely benign not provided 2023-09-21 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV003421940 SCV005211182 likely benign not provided criteria provided, single submitter not provided

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