Submissions for variant NM_024675.4(PALB2):c.34GAG[1] (p.Glu13del)

dbSNP: rs745444171

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000219523	SCV000275795	uncertain significance	Hereditary cancer-predisposing syndrome	2023-03-03	criteria provided, single submitter	clinical testing	The c.37_39delGAG variant (also known as p.E13DEL) located in coding exon 1 of the PALB2 gene. This variant results from an in-frame GAG deletion between nucleotide positions 37 and 39. This results in the in-frame deletion of a glutamic acid residue at codon 13. This amino acid position is highly conserved through mammals. In addition, this alteration is predicted to be deleterious 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000817877	SCV000958462	uncertain significance	Familial cancer of breast	2024-12-18	criteria provided, single submitter	clinical testing	This variant, c.37_39del, results in the deletion of 1 amino acid(s) of the PALB2 protein (p.Glu13del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs745444171, gnomAD 0.01%). 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: 231830). 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	RCV000985894	SCV001134556	uncertain significance	not provided	2019-01-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001175516	SCV001339122	uncertain significance	not specified	2020-03-20	criteria provided, single submitter	clinical testing	Variant summary: PALB2 c.37_39delGAG (p.Glu13del) results in an in-frame deletion that is predicted to remove 1 amino acid from the encoded protein. The variant allele was found at a frequency of 8.1e-06 in 247884 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.37_39delGAG in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. A co-occurrence with a pathogenic variant has been reported (BRCA1 c.4357+1G>A; Internal testing). Four ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Color Diagnostics, LLC DBA Color Health	RCV000219523	SCV001354812	uncertain significance	Hereditary cancer-predisposing syndrome	2023-01-03	criteria provided, single submitter	clinical testing	This variant causes the deletion of one amino acid, glutamic acid, at codon 13 in 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 2/247884 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.
Baylor Genetics	RCV000817877	SCV004202607	uncertain significance	Familial cancer of breast	2024-03-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000985894	SCV005377199	uncertain significance	not provided	2023-11-19	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of one 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; This variant is associated with the following publications: (PMID: 19369211, 20871615)
3DMed Clinical Laboratory Inc	RCV000677894	SCV000804055	uncertain significance	Infiltrating duct carcinoma of breast	2017-07-29	no assertion criteria provided	clinical testing