ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.2816T>G (p.Leu939Trp) (rs45478192)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 21
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000417395 SCV000150001 benign not specified 2017-12-28 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 RCV000114561 SCV000166658 benign Familial cancer of breast 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000116092 SCV000172799 benign Hereditary cancer-predisposing syndrome 2014-08-20 criteria provided, single submitter clinical testing No disease association in appropriately sized case-control study(ies);Internal frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Cancer Genetics Laboratory,Peter MacCallum Cancer Centre RCV000114561 SCV000268019 uncertain significance Familial cancer of breast 2015-06-01 criteria provided, single submitter case-control
Illumina Clinical Services Laboratory,Illumina RCV000306515 SCV000396085 likely benign Fanconi anemia, complementation group N 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000116092 SCV000396086 likely benign Hereditary cancer-predisposing syndrome 2016-06-14 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000417395 SCV000539986 uncertain significance not specified 2016-10-27 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant has been seen in multiple individuals with breast cancer. It is present in ExAC with a MaxMAF of 0.16%. It is classified in ClinVar with 1 star by multiple submitters: VUS by GeneDx and Peter MacCallum Cancer center, and LB/B by Invitae and Ambry.
Genetic Services Laboratory, University of Chicago RCV000417395 SCV000596219 likely benign not specified 2017-01-13 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000417395 SCV000601772 uncertain significance not specified 2017-05-08 criteria provided, single submitter clinical testing
Color RCV000116092 SCV000685981 benign Hereditary cancer-predisposing syndrome 2015-11-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586156 SCV000699576 benign not provided 2016-04-11 criteria provided, single submitter clinical testing Variant summary: The c.2816T>G variant affects a conserved nucleotide, resulting in amino acid change from Leu to Trp. 4/4 in-silico tools predict damaging outcome for this variant (SNPs&GO not captured due to low reliability index). However, these predictions have not been validated via in vitro/vivo functional studies yet. This variant is found in 130/130096 control chromosomes at a frequency of 0.0009993, which is about 6 times of the maximal expected frequency of a pathogenic allele (0.0001563), suggesting this variant is likely a benign polymorphism. This variant has been reported in BRCA1/2 negative BrC/OvC patients without strong evidence for causality. In multiple studies, variant was detected in cases with comparable MAF as in tested controls (Thompson_BCR_2015, Ramus_JNCI_2015, etc) suggesting lack of causative effect. Moreover, there are at least two reported pedigrees showed lack of co-segregation of variant with disease (Damiola_Breast Can Res and Treat_2015), further supporting the neural effect of this variant. In addition, two clinical laboratories via ClinVar classified this variant as benign/likely benign, and one other clinical lab and PALB2 database via ClinVar classified this variant as VUS, all without evidence to independently evaluate. Taken together, this variant was classified as Benign variant.
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000116092 SCV000747822 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-16 criteria provided, single submitter clinical testing
Counsyl RCV000114561 SCV000786127 likely benign Familial cancer of breast 2018-03-01 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000586156 SCV000807098 likely benign not provided 2017-01-12 criteria provided, single submitter clinical testing
Mendelics RCV000116092 SCV000839013 likely benign Hereditary cancer-predisposing syndrome 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000114561 SCV001139996 likely benign Familial cancer of breast 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000417395 SCV001159558 likely benign not specified 2019-03-08 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000586156 SCV001245836 uncertain significance not provided 2019-12-01 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170349 SCV001332923 likely benign Breast and/or ovarian cancer 2019-04-09 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000116092 SCV000886699 likely benign Hereditary cancer-predisposing syndrome 2018-11-19 no assertion criteria provided clinical testing
Leiden Open Variation Database RCV000586156 SCV001193292 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.