Submissions for variant NM_024675.4(PALB2):c.3027del (p.Glu1010fs)

dbSNP: rs876659378

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000217162	SCV000275766	pathogenic	Hereditary cancer-predisposing syndrome	2022-12-15	criteria provided, single submitter	clinical testing	The c.3027delT pathogenic mutation, located in coding exon 10 of the PALB2 gene, results from a deletion of one nucleotide at nucleotide position 3027, causing a translational frameshift with a predicted alternate stop codon (p.E1010Rfs*5). 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	RCV000217162	SCV000690894	pathogenic	Hereditary cancer-predisposing syndrome	2022-03-16	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 10 of the PALB2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in a male individual affected with breast and prostate cancer (PMID: 30564542). 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 (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Invitae	RCV000689332	SCV000816978	pathogenic	Familial cancer of breast	2024-01-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu1010Argfs*5) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 32339256, 35264596). ClinVar contains an entry for this variant (Variation ID: 231807). For these reasons, this variant has been classified as Pathogenic.
Mendelics	RCV000689332	SCV001139989	pathogenic	Familial cancer of breast	2019-05-28	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000689332	SCV004188541	pathogenic	Familial cancer of breast	2023-09-14	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.