Submissions for variant NM_000202.8(IDS):c.418+1G>C

dbSNP: rs1602748255

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000823054	SCV000963892	pathogenic	Mucopolysaccharidosis, MPS-II	2018-08-20	criteria provided, single submitter	clinical testing	This variant has been observed in individuals affected with mucopolysaccharidosis type II (PMID: 16699754, Invitae). For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in IDS are known to be pathogenic (PMID: 8940265, 9875019). Experimental studies have shown that this splice variant disrupts regular splicing (PMID: 16699754). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 3 of the IDS gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV000823054	SCV005089047	pathogenic	Mucopolysaccharidosis, MPS-II	2024-06-07	criteria provided, single submitter	literature only	Null variant (PVS1_VeryStrong), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Patient’s phenotype or family history highly specific for the disease (PP4_Strong)