ClinVar Miner

Submissions for variant NM_024675.3(PALB2):c.2835-1G>A (rs515726099)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000454148 SCV000538161 likely pathogenic Hereditary cancer-predisposing syndrome 2017-12-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
GeneDx RCV000255033 SCV000322681 likely pathogenic not provided 2018-05-16 criteria provided, single submitter clinical testing This variant is denoted PALB2 c.2835-1G>A or IVS8-1G>A and consists of a G>A nucleotidesubstitution at the -1 position of intron 8 of the PALB2 gene. This variant destroys a canonical splice acceptor site andis predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. Although this specific variant has not, to our knowledge,been reported in the literature, an alternate splice variant at this same position, PALB2 c.2835-1G>C has beenobserved in multiple cases of breast cancer, as well as in an individual with a history of ovarian cancer (Casadei 2011,Tischkowitz 2012, Norquist 2015). Based on the currently available information, we consider PALB2 c.2835-1G>A tobe a likely pathogenic variant.
Invitae RCV000168057 SCV000218710 likely pathogenic Familial cancer of breast 2014-10-15 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 8 and is expected to disrupt mRNA splicing. While this particular sequence change has not been reported in the literature, splice site changes in PALB2 are known to be pathogenic. A different nucleotide change at this position, c.2835-1G>C, has been reported in patients affected with breast cancer (PMID: 21285249, 22241545). For these reasons, this sequence change has been classified as Likely Pathogenic.

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