ClinVar Miner

Submissions for variant NM_022455.5(NSD1):c.5892+1G>T

dbSNP: rs886039579
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255457 SCV000322459 pathogenic not provided 2023-11-27 criteria provided, single submitter clinical testing Identified in multiple unrelated patients with NSD1-related Sotos syndrome referred for genetic testing at GeneDx and in published literature (PMID: 34405946); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 17565729, 34405946)
Labcorp Genetics (formerly Invitae), Labcorp RCV003231617 SCV003439296 pathogenic Sotos syndrome 2022-05-28 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 18 of the NSD1 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 NSD1 are known to be pathogenic (PMID: 12464997, 14571271, 15942875, 16247291). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with Sotos syndrome (PMID: 17565729). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 265497). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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