Submissions for variant NM_024675.4(PALB2):c.3351-1G>C

dbSNP: rs1597062406

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001020063	SCV001181492	likely pathogenic	Hereditary cancer-predisposing syndrome	2022-10-11	criteria provided, single submitter	clinical testing	The c.3351-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 13 of the PALB2 gene. This alteration was detected in a patient with ovarian cancer diagnosed at age 60 (Yoo J et al. Ann Lab Med, 2020 Mar;40:148-154). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). 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.
Myriad Genetics, Inc.	RCV003455108	SCV004188430	likely pathogenic	Familial cancer of breast	2023-09-15	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.