ClinVar Miner

Submissions for variant NM_024675.3(PALB2):c.2748+1G>T (rs753153576)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165555 SCV000216287 likely pathogenic Hereditary cancer-predisposing syndrome 2016-10-06 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 RCV000487378 SCV000567121 pathogenic not provided 2015-07-10 criteria provided, single submitter clinical testing This pathogenic variant is denoted PALB2 c.2748+1G>T or IVS7+1G>T and consists of a G>T nucleotide substitution at the +1 position of intron 7 of the PALB2 gene. The variant destroys a canonical splice donor 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 the current evidence, we consider PALB2 c.2748+1G>T to be pathogenic.
Invitae RCV000635768 SCV000757190 likely pathogenic Familial cancer of breast 2018-07-30 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 of the PALB2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs753153576, ExAC 0.001%). This variant has not been reported in the literature in individuals with PALB2-related disease. ClinVar contains an entry for this variant (Variation ID: 186035). 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.
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000635768 SCV000840035 likely pathogenic Familial cancer of breast 2018-02-25 criteria provided, single submitter clinical testing The c.2748+1G>T variant in the PALB2 gene is predicted to disrupt a canonical splice donor site and thus alter mRNA splicing. This variant is extremely rare in the general population. This c.2748+1G>T variant in the PALB2 gene is classified as likely pathogenic.

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