Submissions for variant NM_000202.8(IDS):c.748G>A (p.Ala250Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV004547259	SCV005042668	uncertain significance	Mucopolysaccharidosis, MPS-II		criteria provided, single submitter	clinical testing	The missense c.748G>A p.Ala250Thr variant in the IDS gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency 0.0005% in the gnomAD Exomes and novel in 1000 Genomes. The amino acid Alanine at position 250 is changed to a Threonine changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Ala250Thr in IDS is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV004547259	SCV005201018	likely pathogenic	Mucopolysaccharidosis, MPS-II	2022-12-12	criteria provided, single submitter	clinical testing	A hemizygous missense variant in exon 6 of the IDS gene that results in the amino acid substitution of Threonine for Alanine at codon 250 was detected. The observed variant c.748G>A has not been reported in the 1000 genomes and has a minor allele frequency of 0.00055% in the gnomAD database. The in silico prediction of the variant are possibly damaging by LRT and FATHMM. In summary, the variant meets our criteria to be classified as likely pathogenic.