ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.909C>T (p.Leu303=)

gnomAD frequency: 0.00101  dbSNP: rs145788619
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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212781 SCV000170865 benign not specified 2013-11-23 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 RCV000127304 SCV000212828 likely benign Hereditary cancer-predisposing syndrome 2014-08-07 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000114670 SCV000252867 benign Familial cancer of breast 2024-02-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000212781 SCV000314379 likely benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000127304 SCV000396124 likely benign Hereditary cancer-predisposing syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000300127 SCV000396125 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Counsyl RCV000114670 SCV000488221 likely benign Familial cancer of breast 2016-01-27 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000127304 SCV000686081 likely benign Hereditary cancer-predisposing syndrome 2015-10-26 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001531848 SCV001747153 likely benign not provided 2021-03-01 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000212781 SCV002069350 likely benign not specified 2019-03-28 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000127304 SCV002531234 likely benign Hereditary cancer-predisposing syndrome 2021-03-29 criteria provided, single submitter curation
Myriad Genetics, Inc. RCV000114670 SCV004019644 benign Familial cancer of breast 2023-03-31 criteria provided, single submitter clinical testing This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001531848 SCV004563615 benign not provided 2023-11-14 criteria provided, single submitter clinical testing
Leiden Open Variation Database RCV000114670 SCV001193038 likely benign Familial cancer of breast 2019-05-13 no assertion criteria provided curation Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001358321 SCV001554021 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The PALB2 p.Leu303= variant was identified in 2 of 5770 proband chromosomes (frequency: 0.0003) from individuals or families with prostate or breast cancer and was not identified in 520 control chromosomes from healthy individuals (Tischkowitz 2008, Zheng 2012). The variant was also identified in dbSNP (ID: rs145788619) as "With other allele", ClinVar (classified as benign by GeneDx and Invitae; as likely benign by Ambry Genetics, Counsyl, Color Genomics and one other clinical laboratory), and in LOVD 3.0 database (2x). The variant was not identified in Cosmic, MutDB, or the Zhejiang University database. The variant was identified in control databases in 96 of 277112 chromosomes at a frequency of 0.0003, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 86 of 24026 chromosomes (freq: 0.004), Latino in 9 of 34418 chromosomes (freq: 0.0003), and European in 1 of 126634 chromosomes (freq: 0.000008); it was not observed in the Other, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Leu303= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000212781 SCV002035291 benign not specified no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001531848 SCV002036796 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001531848 SCV002037465 likely benign not provided no assertion criteria provided clinical testing

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