rs1557340558

Positions:

• chrX-149505034-CCTGTGGTCGAGTTGGCCTGCGTTTCGGATCCGAGGGCGACGCAGACGGAGCTCAGAACCAGACCCAGCCAGAGAAGGCCTCGGCCGGTCCGGGGTGGCGGCATTTCGGCTTCGACGCGGCCGCTTCAGAGCGGCGGGGACAGGCTGCAGCAGGTGGCGCAGTTAGCAGCCGCCGCCGCAGCCACAGAGACCTCCTCGTCGGGAACCCATGAAGACTGCGCAACACAGCCGCCGCCCGGGCCCGCAGGCCCGGGCGCTGGCCGCAGCGCGAGTGCGTCCGTGCGACTCTTCCCTGCGTCCCTCCCCTCCGGGGCGGGTTCT-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_000202.8(IDS):​c.-217_103del variant causes a 5 prime UTR truncation, exon loss change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: IDS NM_000202.8 5_prime_UTR_truncation, exon_loss
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.63

Genes affected

IDS (HGNC:5389): (iduronate 2-sulfatase) This gene encodes a member of the sulfatase family of proteins. The encoded preproprotein is proteolytically processed to generate two polypeptide chains. This enzyme is involved in the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations in this gene are associated with the X-linked lysosomal storage disease mucopolysaccharidosis type II, also known as Hunter syndrome. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

ENSG00000241489 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-149505034-CCTGTGGTCGAGTTGGCCTGCGTTTCGGATCCGAGGGCGACGCAGACGGAGCTCAGAACCAGACCCAGCCAGAGAAGGCCTCGGCCGGTCCGGGGTGGCGGCATTTCGGCTTCGACGCGGCCGCTTCAGAGCGGCGGGGACAGGCTGCAGCAGGTGGCGCAGTTAGCAGCCGCCGCCGCAGCCACAGAGACCTCCTCGTCGGGAACCCATGAAGACTGCGCAACACAGCCGCCGCCCGGGCCCGCAGGCCCGGGCGCTGGCCGCAGCGCGAGTGCGTCCGTGCGACTCTTCCCTGCGTCCCTCCCCTCCGGGGCGGGTTCT-C is Pathogenic according to our data. Variant chrX-149505034-CCTGTGGTCGAGTTGGCCTGCGTTTCGGATCCGAGGGCGACGCAGACGGAGCTCAGAACCAGACCCAGCCAGAGAAGGCCTCGGCCGGTCCGGGGTGGCGGCATTTCGGCTTCGACGCGGCCGCTTCAGAGCGGCGGGGACAGGCTGCAGCAGGTGGCGCAGTTAGCAGCCGCCGCCGCAGCCACAGAGACCTCCTCGTCGGGAACCCATGAAGACTGCGCAACACAGCCGCCGCCCGGGCCCGCAGGCCCGGGCGCTGGCCGCAGCGCGAGTGCGTCCGTGCGACTCTTCCCTGCGTCCCTCCCCTCCGGGGCGGGTTCT-C is described in ClinVar as [Pathogenic]. Clinvar id is 221979.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDS	NM_000202.8	c.-217_103del		5_prime_UTR_truncation, exon_loss_variant	1/9	ENST00000340855.11	NP_000193.1
IDS	NM_000202.8	c.-217_103del		exon_loss_variant, splice_region_variant	1/9	ENST00000340855.11	NP_000193.1
IDS	NM_000202.8	c.-217_103del		upstream_gene_variant		ENST00000340855.11	NP_000193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IDS	ENST00000340855.11	c.-217_103del		5_prime_UTR_truncation, exon_loss_variant	1/9	1	NM_000202.8	ENSP00000339801.6
IDS	ENST00000340855.11	c.-217_103del		exon_loss_variant, splice_region_variant	1/9	1	NM_000202.8	ENSP00000339801.6
ENSG00000241489	ENST00000651111.1	c.-215-4317_-215-3998del		intron_variant				ENSP00000498395.1
IDS	ENST00000340855.11	c.-217_103del		upstream_gene_variant		1	NM_000202.8	ENSP00000339801.6

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mucopolysaccharidosis, MPS-II Pathogenic:1

Pathogenic, criteria provided, single submitter

research

MOLECULAR BIOLOGY LABORATORY, INSTITUTO NACIONAL DE PEDIATRIA

Oct 18, 2015

Pathogenic variation identified in a Hunter syndrome male patient with I2S deficiency. He presents mental retardation, but no seizures, nor hydrocephaly. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1557340558; hg19: chrX-148586564;