Submissions for variant NM_024675.4(PALB2):c.1039G>T (p.Glu347Ter)

dbSNP: rs1060499812

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000454356	SCV000538133	pathogenic	Hereditary cancer-predisposing syndrome	2023-12-20	criteria provided, single submitter	clinical testing	The p.E347* pathogenic mutation (also known as c.1039G>T), located in coding exon 4 of the PALB2 gene, results from a G to T substitution at nucleotide position 1039. This changes the amino acid from a glutamic acid to a stop codon within coding exon 4. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Color Diagnostics, LLC DBA Color Health	RCV000454356	SCV001356014	pathogenic	Hereditary cancer-predisposing syndrome	2022-03-08	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 4 of the PALB2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PALB2 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003239290	SCV003936131	pathogenic	Familial cancer of breast	2023-07-05	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 4 of the PALB2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or nonfunctional protein product. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PALB2 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315427	SCV004015166	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 5	2023-07-07	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 4 of the PALB2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or nonfunctional protein product. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PALB2 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.
Myriad Genetics, Inc.	RCV003239290	SCV004189458	pathogenic	Familial cancer of breast	2023-09-07	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Baylor Genetics	RCV003239290	SCV004202092	pathogenic	Familial cancer of breast	2023-09-07	criteria provided, single submitter	clinical testing