Submissions for variant NM_024675.4(PALB2):c.212-10del

dbSNP: rs766487430

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084305	SCV000252859	benign	Familial cancer of breast	2025-01-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000587569	SCV000565340	likely benign	not provided	2021-02-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000580912	SCV000685919	likely benign	Hereditary cancer-predisposing syndrome	2016-04-04	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587569	SCV000699554	uncertain significance	not provided	2017-05-26	criteria provided, single submitter	clinical testing	Variant summary: The PALB2 c.212-10delT variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts no alterations to ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC in 3 of 64868 control chromosomes from all ethnicities, but was predominantly observed in the African subpopulation at a frequency of 0.000315 (2/6352). This frequency is about 2 times the estimated maximal expected allele frequency of a pathogenic PALB2 variant (0.0001563), suggesting this may be a benign polymorphism found primarily in the populations of African origin. In addition, two clinical diagnostic laboratories have classified this variant as likely benign or benign. To our knowledge, the variant of interest has not been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS)-possibly benign until additional information becomes available.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000587569	SCV001469592	uncertain significance	not provided	2024-01-05	criteria provided, single submitter	clinical testing	The PALB2 c.212-10del variant has not been reported in individuals with PALB2-related conditions in the published literature. The frequency of this variant in the general population, 0.00057 (12/21208 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect PALB2 mRNA splicing. Based on the available information, we are unable to determine the clinical significance of this variant.
Genetic Services Laboratory, University of Chicago	RCV001818473	SCV002066877	likely benign	not specified	2021-02-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587569	SCV002506124	likely benign	not provided	2022-01-04	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000580912	SCV002530671	likely benign	Hereditary cancer-predisposing syndrome	2021-11-27	criteria provided, single submitter	curation
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000580912	SCV002819251	likely benign	Hereditary cancer-predisposing syndrome	2022-12-20	criteria provided, single submitter	clinical testing