Submissions for variant NM_024675.4(PALB2):c.3010C>T (p.Gln1004Ter)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV003450466	SCV004188545	pathogenic	Familial cancer of breast	2023-09-14	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.
Invitae	RCV003450466	SCV004334719	pathogenic	Familial cancer of breast	2023-09-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1004*) 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 variant has not been reported in the literature in individuals affected with PALB2-related conditions. For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV003585399	SCV004357826	pathogenic	Hereditary cancer-predisposing syndrome	2021-07-07	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 10 of the PALB2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, 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 (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.