Submission Details

NSD2 was first reported in relation to autosomal dominant NSD2-Wolf-Hirschhorn syndrome in 2017 (28600779: Monies et al. 2017). At least six unique de novo, loss-of -function variants have been reported in the literature. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least six probands from three publications (29892088: Derar et al. 2018; 29760529: Lozier et al. 2018; 31171569: Barrie et al. 2019). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism for disease is loss of function (31171569: Barrie et al. 2019). This gene-disease relationship is supported by expression studies, which show that fetal brain contained the most complex pattern of transcripts and is expressed in mouse brain, ganglia, neural tube, jaw, frontal face region, intestinal and lung epithelium, liver, adrenals, and the urogenital system (9618163: Stec et al. 1998). In addition, Whsc1-deficient heterozygote mice present with severe growth and craniofacial defects (19483677: Nimura et al. 2009). In summary, NSD2 is definitively associated with autosomal dominant NSD2-Wolf-Hirschhorn syndrome.

PubMed IDs:

29892088 29760529 31171569 9618163 19483677

Assertion Criteria:

Click here to view assertion criteria

https://www.clinicalgenome.org/site/assets/files/3975/gene-disease_validity_standard_operating_procedures_version_7-1.pdf

Submitter Submitted Date:

10/15/2020

The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).

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