ClinVar Miner

Submissions for variant NM_024675.3(PALB2):c.1492G>T (p.Asp498Tyr) (rs75023630)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000160870 SCV000215553 benign Hereditary cancer-predisposing syndrome 2014-12-30 criteria provided, single submitter clinical testing
Cancer Genetics Laboratory,Peter MacCallum Cancer Centre RCV000197379 SCV000268000 uncertain significance Familial cancer of breast 2015-06-01 criteria provided, single submitter case-control
Color RCV000160870 SCV000685885 likely benign Hereditary cancer-predisposing syndrome 2015-01-22 criteria provided, single submitter clinical testing
GeneDx RCV000200991 SCV000211557 likely benign not specified 2017-12-22 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.
Illumina Clinical Services Laboratory,Illumina RCV000160870 SCV000396111 likely benign Hereditary cancer-predisposing syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000368837 SCV000396112 likely benign Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000200991 SCV000917958 likely benign not specified 2018-08-13 criteria provided, single submitter clinical testing Variant summary: PALB2 c.1492G>T (p.Asp498Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 40-fold above the estimated maximal expected allele frequency for a pathogenic variant in PALB2 causing Hereditary Breast and Ovarian Cancer phenotype (0.00016), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.1492G>T has been identified in individuals affected with Hereditary Breast and Ovarian Cancer without strong evidence for causality. No experimental evidence demonstrating the variants impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 with conflicting assessments, including benign (1x), likely benign (3x), and uncertain significance (2x). Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000197379 SCV000253582 benign Familial cancer of breast 2018-01-08 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000200991 SCV000601730 uncertain significance not specified 2016-10-24 criteria provided, single submitter clinical testing

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