Submissions for variant NM_024675.4(PALB2):c.2507_2509del (p.Val836del)

dbSNP: rs587782697

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000132137	SCV000187208	uncertain significance	Hereditary cancer-predisposing syndrome	2022-12-05	criteria provided, single submitter	clinical testing	The c.2507_2509delTCG variant (also known as p.V836del) is located in coding exon 5 of the PALB2 gene. This variant results from an in-frame TCG deletion at nucleotide positions 2507 to 2509. This results in the in-frame deletion of a valine at codon 836. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be inconclusive by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV000656935	SCV000292658	uncertain significance	not provided	2024-05-13	criteria provided, single submitter	clinical testing	In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28825729, 24485656, 19609323)
Illumina Laboratory Services, Illumina	RCV000354505	SCV000396092	uncertain significance	Fanconi anemia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000132137	SCV000396093	uncertain significance	Hereditary cancer-predisposing syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000465007	SCV000550625	uncertain significance	Familial cancer of breast	2024-11-11	criteria provided, single submitter	clinical testing	This variant, c.2507_2509del, results in the deletion of 1 amino acid(s) of the PALB2 protein (p.Val836del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs587782697, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 142756). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000656935	SCV000601763	uncertain significance	not provided	2020-07-16	criteria provided, single submitter	clinical testing
Counsyl	RCV000465007	SCV000784949	uncertain significance	Familial cancer of breast	2017-02-16	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000132137	SCV000903544	uncertain significance	Hereditary cancer-predisposing syndrome	2023-01-10	criteria provided, single submitter	clinical testing	This variant deletes a single amino acid from the PALB2 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250508 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Myriad Genetics, Inc.	RCV000465007	SCV004019690	likely benign	Familial cancer of breast	2023-03-31	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].
Baylor Genetics	RCV000465007	SCV005053894	uncertain significance	Familial cancer of breast	2024-02-13	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005016454	SCV005646479	uncertain significance	Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3; Breast-ovarian cancer, familial, susceptibility to, 5	2024-02-14	criteria provided, single submitter	clinical testing