rs1557340286

Variant names:

• chrX-149503478-G-A
• rs1557340286
• NM_000202.8:c.252C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-149503478-G-A
• chrX-149503478-G-C
• chrX-149503478-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000202.8(IDS):​c.252C>T​(p.Cys84Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000296 in 1,013,538 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000030 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: IDS NM_000202.8 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0810
• Publications: 0 publications found

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]

IDS Gene-Disease associations (from GenCC):

• mucopolysaccharidosis type 2

  Inheritance: XL, AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, PanelApp Australia, Myriad Women’s Health
• mucopolysaccharidosis type 2, attenuated form

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• mucopolysaccharidosis type 2, severe form

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000241489 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant X-149503478-G-A is Benign according to our data. Variant chrX-149503478-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1137279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.081 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000202.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDS	NM_000202.8	MANE Select	c.252C>T	p.Cys84Cys	synonymous	Exon 3 of 9	NP_000193.1
	IDS	NM_006123.5		c.252C>T	p.Cys84Cys	synonymous	Exon 3 of 8	NP_006114.1
	IDS	NR_104128.2		n.421C>T		non_coding_transcript_exon	Exon 3 of 9

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDS	ENST00000340855.11	TSL:1 MANE Select	c.252C>T	p.Cys84Cys	synonymous	Exon 3 of 9	ENSP00000339801.6
	IDS	ENST00000370441.8	TSL:1	c.252C>T	p.Cys84Cys	synonymous	Exon 3 of 8	ENSP00000359470.4
	IDS	ENST00000466323.5	TSL:1	n.252C>T		non_coding_transcript_exon	Exon 3 of 9	ENSP00000418264.1

Frequencies

GnomAD3 genomes AF: 0.00000904 AC: 1 AN: 110583 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000332

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000904 AC: 1 AN: 110674 AF XY: 0.0000288

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000234

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000296 AC: 3 AN: 1013538 Hom.: 0 Cov.: 23 AF XY: 0.00000329 AC XY: 1 AN XY: 303518

African (AFR) AF: 0.00 AC: 0 AN: 24814

American (AMR) AF: 0.00 AC: 0 AN: 29082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18446

East Asian (EAS) AF: 0.00 AC: 0 AN: 28873

South Asian (SAS) AF: 0.00 AC: 0 AN: 49761

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38713

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3099

European-Non Finnish (NFE) AF: 0.00000257 AC: 2 AN: 777477

Other (OTH) AF: 0.0000231 AC: 1 AN: 43273

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000904 AC: 1 AN: 110583 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 32803

African (AFR) AF: 0.0000332 AC: 1 AN: 30145

American (AMR) AF: 0.00 AC: 0 AN: 10535

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2634

East Asian (EAS) AF: 0.00 AC: 0 AN: 3506

South Asian (SAS) AF: 0.00 AC: 0 AN: 2593

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6001

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52770

Other (OTH) AF: 0.00 AC: 0 AN: 1482

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Mucopolysaccharidosis, MPS-II (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.4
DANN	Benign	0.94
PhyloP100		-0.081

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1557340286; hg19: chrX-148585008;