ClinVar Miner

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

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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.
Ambry Genetics RCV000160870 SCV000215553 benign Hereditary cancer-predisposing syndrome 2014-12-30 criteria provided, single submitter clinical testing
Invitae RCV000197379 SCV000253582 benign Familial cancer of breast 2019-12-31 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
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, complementation group N 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000858743 SCV000601730 likely benign not provided 2019-03-20 criteria provided, single submitter clinical testing
Color RCV000160870 SCV000685885 likely benign Hereditary cancer-predisposing syndrome 2015-01-22 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.
Cancer Genomics Group,Japanese Foundation For Cancer Research RCV001030650 SCV001193681 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research
CeGaT Praxis fuer Humangenetik Tuebingen RCV000858743 SCV001247803 uncertain significance not provided 2019-10-01 criteria provided, single submitter clinical testing
Leiden Open Variation Database RCV000858743 SCV001193114 likely benign not provided 2019-05-13 no assertion criteria provided curation Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitters to LOVD: Marc Tischkowitz, Melissa DeRycke, Yukihide Momozawa.

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