Submissions for variant NM_024675.4(PALB2):c.2834+2T>A

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV003450451	SCV004188450	likely pathogenic	Familial cancer of breast	2023-09-13	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.
Baylor Genetics	RCV003450451	SCV004202761	likely pathogenic	Familial cancer of breast	2022-01-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004364752	SCV005028991	likely pathogenic	Hereditary cancer-predisposing syndrome	2023-10-11	criteria provided, single submitter	clinical testing	The c.2834+2T>A intronic variant results from a T to A substitution two nucleotides after coding exon 8 of the PALB2 gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.