ClinVar Miner

Submissions for variant NM_133433.4(NIPBL):c.6589+5G>A (rs1554032266)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558355 SCV000657503 pathogenic Cornelia de Lange syndrome 1 2017-02-06 criteria provided, single submitter clinical testing This sequence change falls in intron 38 of the NIPBL gene. It does not directly change the encoded amino acid sequence of the NIPBL protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Cornelia de Lange Syndrome (PMID: 20824775, Invitae). In one of these individuals, it was reported to be de novo (PMID: 20824775). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of nucleotide changes on RNA splicing suggest that this c.6589+5G>A variant may alter RNA splicing, although this prediction has not been confirmed by published studies. A different variant affecting this nucleotide (c.6589+5G>C) has been determined to be pathogenic (PMID: 22857006). This suggests that this nucleotide is critical for normal RNA splicing, and that other variants at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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