ClinVar Miner

Submissions for variant NM_001127255.2(NLRP7):c.2130-2A>G

gnomAD frequency: 0.00002  dbSNP: rs764734665
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000778555 SCV000914855 uncertain significance Hydatidiform mole, recurrent, 1 2017-12-18 criteria provided, single submitter clinical testing The NLRP7 c.2130-2A>G splice acceptor variant has been reported in one study and identified in one compound heterozygous individual with at least one partial molar pregnancy and one complete molar pregnancy (Nguyen et al. 2014). Control data are unavailable for this variant which is reported at a frequency of 0.000036 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the limited evidence and the potential impact of splice acceptor variants, the c.2130-2A>G variant is classified as a variant of uncertain significance but suspicious for pathogenicity for recurrent hydatidiform mole. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV001379846 SCV001577727 likely pathogenic not provided 2017-07-30 criteria provided, single submitter clinical testing 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NLRP7 are known to be pathogenic (PMID: 19246479, 19309689). This sequence change affects an acceptor splice site in intron 5 of the NLRP7 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 (rs764734665, ExAC 0.002%). This variant has been reported in the literature in the product of conception from individuals affected with hydatidiform mole (PMID: 25097207) 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.
GeneDx RCV001379846 SCV005325180 uncertain significance not provided 2023-12-23 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25097207)

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