Submissions for variant NM_133433.4(NIPBL):c.64+1G>A

dbSNP: rs587784009

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000146685	SCV000193998	pathogenic	Cornelia de Lange syndrome 1	2013-02-08	criteria provided, single submitter	clinical testing
Invitae	RCV000146685	SCV000657502	pathogenic	Cornelia de Lange syndrome 1	2023-06-07	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 159191). Disruption of this splice site has been observed in individual(s) with Cornelia de Lange syndrome (PMID: 15591270, 22581668, 25574841). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This sequence change affects a donor splice site in intron 2 of the NIPBL gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NIPBL are known to be pathogenic (PMID: 15318302, 19763162, 23505322, 29995837).
Genome-Nilou Lab	RCV000146685	SCV002055955	pathogenic	Cornelia de Lange syndrome 1	2021-07-15	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000146685	SCV002061787	pathogenic	Cornelia de Lange syndrome 1	2021-12-10	criteria provided, single submitter	clinical testing	PVS1, PS4, PM2, PM6
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000146685	SCV000195837	pathogenic	Cornelia de Lange syndrome 1	2014-12-02	no assertion criteria provided	research