ClinVar Miner

Submissions for variant NM_024675.3(PALB2):c.3114-1G>A (rs886039619)

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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 RCV000569707 SCV000666942 likely pathogenic Hereditary cancer-predisposing syndrome 2016-11-16 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 RCV000255848 SCV000322537 likely pathogenic not provided 2016-08-16 criteria provided, single submitter clinical testing This variant is denoted PALB2 c.3114-1G>A or IVS10-1G>A and consists of a G>A nucleotide substitution at the -1 position of intron 10 of the PALB2 gene. This variant destroys a canonical splice acceptor site and is 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. This variant has not, to our knowledge, been published in the literature. Based on currently available evidence, we consider PALB2 c.3114-1G>A to be a likely pathogenic variant.
Invitae RCV000551424 SCV000633403 likely pathogenic Familial cancer of breast 2018-11-06 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 10 of the PALB2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with breast cancer (PMID: 28825143). ClinVar contains an entry for this variant (Variation ID: 265552). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 24136930, 25099575). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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