ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.48+1G>C

dbSNP: rs515726118
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213648 SCV000274677 likely pathogenic Hereditary cancer-predisposing syndrome 2015-03-16 criteria provided, single submitter clinical testing The c.48+1G>C intronic variant results from a G to C substitution one nucleotide after coding exon 1 of the PALB2 gene. This variant was first reported in an individual with breast cancer and family history of breast cancer (Hellebrand H, et al. Hum. Mutat. 2011 Jun; 32(6):E2176-88). Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native donor splice site; however, direct evidence is unavailable. 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.
GeneDx RCV000236723 SCV000293389 uncertain significance not provided 2015-12-22 criteria provided, single submitter clinical testing This variant is denoted PALB2 c.48+1G>C or IVS1+1G>C and consists of a G>C nucleotide substitution at the +1 position of intron 1 of the PALB2 gene. This variant destroys a canonical splice donor site and is predicted to cause skipping of exon 2, resulting in an in-frame deletion of 20 amino acids that are not part of a critical functional domain. This variant has been reported in an individual with a personal and family history of breast cancer (Hellebrand 2011). Based on the current evidence, we consider PALB2 c.48+1G>C to be a variant of uncertain significance.
Myriad Genetics, Inc. RCV001030106 SCV004019437 likely pathogenic Familial cancer of breast 2023-03-01 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.
Leiden Open Variation Database RCV001030106 SCV001192906 likely pathogenic Familial cancer of breast 2019-05-13 no assertion criteria provided curation Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitters to LOVD: Alfons Meindl, Marc Tischkowitz.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.