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rs1557340558

chrX-149505034-CCTGTGGTCGAGTTGGCCTGCGTTTCGGATCCGAGGGCGACGCAGACGGAGCTCAGAACCAGACCCAGCCAGAGAAGGCCTCGGCCGGTCCGGGGTGGCGGCATTTCGGCTTCGACGCGGCCGCTTCAGAGCGGCGGGGACAGGCTGCAGCAGGTGGCGCAGTTAGCAGCCGCCGCCGCAGCCACAGAGACCTCCTCGTCGGGAACCCATGAAGACTGCGCAACACAGCCGCCGCCCGGGCCCGCAGGCCCGGGCGCTGGCCGCAGCGCGAGTGCGTCCGTGCGACTCTTCCCTGCGTCCCTCCCCTCCGGGGCGGGTTCT-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The X-149505034-CCTGTGGTCGAGTTGGCCTGCGTTTCGGATCCGAGGGCGACGCAGACGGAGCTCAGAACCAGACCCAGCCAGAGAAGGCCTCGGCCGGTCCGGGGTGGCGGCATTTCGGCTTCGACGCGGCCGCTTCAGAGCGGCGGGGACAGGCTGCAGCAGGTGGCGCAGTTAGCAGCCGCCGCCGCAGCCACAGAGACCTCCTCGTCGGGAACCCATGAAGACTGCGCAACACAGCCGCCGCCCGGGCCCGCAGGCCCGGGCGCTGGCCGCAGCGCGAGTGCGTCCGTGCGACTCTTCCCTGCGTCCCTCCCCTCCGGGGCGGGTTCT-C variant causes a splice region, coding sequence, 5 prime UTR 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 splice_region, coding_sequence, 5_prime_UTR

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.63
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PP5
?
    PP5 - Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation
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 UniProt
IDSNM_000202.8 linkuse as main transcript splice_region_variant, coding_sequence_variant, 5_prime_UTR_variant 1/9 ENST00000340855.11
IDSNM_001166550.4 linkuse as main transcript splice_region_variant, 5_prime_UTR_variant 1/9
IDSNM_006123.5 linkuse as main transcript splice_region_variant, coding_sequence_variant, 5_prime_UTR_variant 1/8
IDSNR_104128.2 linkuse as main transcript splice_region_variant, non_coding_transcript_exon_variant 1/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IDSENST00000340855.11 linkuse as main transcript splice_region_variant, coding_sequence_variant, 5_prime_UTR_variant 1/91 NM_000202.8 P1P22304-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
22
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
22

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Mucopolysaccharidosis, MPS-II Pathogenic:1
Pathogenic, criteria provided, single submitterresearchMOLECULAR BIOLOGY LABORATORY, INSTITUTO NACIONAL DE PEDIATRIAOct 18, 2015Pathogenic 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

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1557340558; hg19: chrX-148586564; API