Submissions for variant NM_024675.4(PALB2):c.2365C>T (p.Leu789=)

gnomAD frequency: 0.00099  dbSNP: rs145805054

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212810	SCV000211490	benign	not specified	2014-06-10	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	RCV000160817	SCV000213606	likely benign	Hereditary cancer-predisposing syndrome	2014-12-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Invitae	RCV001030300	SCV000252862	benign	Familial cancer of breast	2024-02-01	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000588448	SCV000601757	benign	not provided	2023-08-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000160817	SCV000685945	likely benign	Hereditary cancer-predisposing syndrome	2015-12-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588448	SCV000699563	benign	not provided	2016-09-16	criteria provided, single submitter	clinical testing	Variant summary: The PALB2 c.2365C>T (p.Leu789Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 42/121310 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0036538 (38/10400). This frequency is about 23 times the estimated maximal expected allele frequency of a pathogenic PALB2 variant (0.0001563), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as Benign.
Eurofins Ntd Llc (ga)	RCV000212810	SCV000859962	likely benign	not specified	2018-03-21	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798298	SCV002043594	likely benign	Breast and/or ovarian cancer	2020-04-22	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000212810	SCV002070563	likely benign	not specified	2018-04-18	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000160817	SCV002530693	likely benign	Hereditary cancer-predisposing syndrome	2021-07-23	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000212810	SCV004242688	benign	not specified	2024-02-06	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588448	SCV004562551	benign	not provided	2023-09-21	criteria provided, single submitter	clinical testing
Leiden Open Variation Database	RCV001030300	SCV001193216	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.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000588448	SCV001809795	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000588448	SCV001905901	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000588448	SCV002036091	likely benign	not provided		no assertion criteria provided	clinical testing