Submissions for variant NM_003676.4(DEGS1):c.320G>A (p.Trp107Ter)

Minimum review status:		Collection method:
Minimum conflict level: Report conflict between different conditions
		ClinVar version:

Total submissions: 4

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
SIB Swiss Institute of Bioinformatics	RCV000768574	SCV001146810	likely pathogenic	Leukodystrophy, hypomyelinating, 18	2019-09-25	criteria provided, single submitter	curation	This variant is interpreted as a Likely pathogenic for Leukodystrophy, hypomyelinating, 18, autosomal recessive. The following ACMG Tag(s) were applied: PM2, PVS1-Strong.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000768574	SCV001430792	likely pathogenic	Leukodystrophy, hypomyelinating, 18	2020-05-28	criteria provided, single submitter	research	The homozygous p.Trp107Ter variant in DEGS1 was identified by our study in an individual with hypomyelinating leukodystrophy (PMID: 30620337). The p.Trp107Ter variant in DEGS1 has also been reported in 3 additional individuals with hypomyelinating leukodystrophy, segregated with disease in 3 affected relatives from 1 family (PMID: 30620337), and has been identified in 0.003% (1/30616) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs1382083552). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported pathogenic by OMIM in ClinVar (Variation ID: 626330). The presence of this variant in 4 affected homozygotes increases the likelihood that the p.Trp107Ter variant is pathogenic (PMID: 30620337). This nonsense variant leads to a premature termination codon at position 107, which is predicted to lead to a truncated or absent protein. While there is some evidence to suggest that loss of function of the DEGS1 gene is a disease mechanism in autosomal recessive hypomyelinating leukodystrophy, this association is not yet strongly established based on the criteria laid out in Tayoun, 2018 (PMID: 30192042). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1_Strong, PM2, PM3, PP1 (Richards 2015).
Revvity Omics, Revvity	RCV000768574	SCV003827526	pathogenic	Leukodystrophy, hypomyelinating, 18	2022-07-27	criteria provided, single submitter	clinical testing
OMIM	RCV000768574	SCV000899278	pathogenic	Leukodystrophy, hypomyelinating, 18	2019-04-30	no assertion criteria provided	literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.