Submissions for variant NM_024675.4(PALB2):c.2205dup (p.Ala736fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002425785	SCV002730764	pathogenic	Hereditary cancer-predisposing syndrome	2021-06-28	criteria provided, single submitter	clinical testing	The c.2205dupA pathogenic mutation, located in coding exon 5 of the PALB2 gene, results from a duplication of A at nucleotide position 2205, causing a translational frameshift with a predicted alternate stop codon (p.A736Sfs*9). 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.
Myriad Genetics, Inc.	RCV003454335	SCV004186204	pathogenic	Familial cancer of breast	2023-09-12	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Color Diagnostics, LLC DBA Color Health	RCV002425785	SCV004357879	pathogenic	Hereditary cancer-predisposing syndrome	2023-04-03	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 5 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. To our knowledge, this variant has not been reported in individuals affected with PALB2-related disorders 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.