Submissions for variant NM_024675.4(PALB2):c.1000T>G (p.Tyr334Asp)

gnomAD frequency: 0.00026  dbSNP: rs202241382

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165476	SCV000216207	likely benign	Hereditary cancer-predisposing syndrome	2019-04-29	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	RCV001087026	SCV000290797	benign	Familial cancer of breast	2024-01-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000165476	SCV000396120	likely benign	Hereditary cancer-predisposing syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000402501	SCV000396121	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.
GeneDx	RCV000483117	SCV000565345	uncertain significance	not provided	2023-12-22	criteria provided, single submitter	clinical testing	Observed individuals with breast or pancreatic cancer, as well as in unaffected controls (PMID: 21356067, 25356972); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21356067, 25356972)
Color Diagnostics, LLC DBA Color Health	RCV000165476	SCV000911104	benign	Hereditary cancer-predisposing syndrome	2016-10-27	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000165476	SCV002530574	benign	Hereditary cancer-predisposing syndrome	2022-03-06	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV004595925	SCV005090209	likely benign	not specified	2024-07-31	criteria provided, single submitter	clinical testing
Leiden Open Variation Database	RCV000483117	SCV001193050	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.