ClinVar Miner

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

dbSNP: rs1597062406
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001385043 SCV001584753 pathogenic Familial cancer of breast 2021-03-27 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the PALB2 protein. Other variant(s) that disrupt this region (p.Tyr1183*) have been determined to be pathogenic (PMID: 17200668, 26315354, 17200671, 21365267, 22241545, 19609323). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice site has been observed in individual(s) with ovarian cancer (PMID: 31650731). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in the last intron (intron 12) of the PALB2 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.
Fulgent Genetics, Fulgent Genetics RCV005014535 SCV005646458 likely pathogenic Fanconi anemia complementation group N; Pancreatic cancer, susceptibility to, 3; Breast-ovarian cancer, familial, susceptibility to, 5 2024-06-23 criteria provided, single submitter clinical testing

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