Submissions for variant NM_002076.4(GNS):c.875+2del

gnomAD frequency: 0.00001  dbSNP: rs1219484230

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002538693	SCV003441109	pathogenic	Mucopolysaccharidosis, MPS-III-D	2022-09-19	criteria provided, single submitter	clinical testing	This sequence change affects a splice site in intron 7 of the GNS 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 GNS are known to be pathogenic (PMID: 20232353). This variant is present in population databases (no rsID available, gnomAD 0.007%). Disruption of this splice site has been observed in individual(s) with mucopolysaccharidosis Type IIID (PMID: 20232353). ClinVar contains an entry for this variant (Variation ID: 1299282). 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001725908	SCV001963563	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001725908	SCV001965443	pathogenic	not provided		no assertion criteria provided	clinical testing