X-149485920-C-T

Variant names:

• chrX-149485920-C-T
• rs530501
• NM_000202.8:c.1180+1005G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000202.8(IDS):​c.1180+1005G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 110,637 control chromosomes in the GnomAD database, including 7,307 homozygotes. There are 12,944 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (7307 hom., 12944 hem., cov: 23)
• Consequence: IDS NM_000202.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 8 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 Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDS	NM_000202.8	MANE Select	c.1180+1005G>A		intron	N/A	NP_000193.1	P22304-1
	IDS	NM_001166550.4		c.910+1005G>A		intron	N/A	NP_001160022.1	B4DGD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDS	ENST00000340855.11	TSL:1 MANE Select	c.1180+1005G>A		intron	N/A	ENSP00000339801.6	P22304-1
	ENSG00000241489	ENST00000651111.1		c.547+1005G>A		intron	N/A	ENSP00000498395.1	B3KWA1
	IDS	ENST00000875674.1		c.1261+1005G>A		intron	N/A	ENSP00000545733.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 45034 AN: 110586 Hom.: 7317 Cov.: 23

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.0180

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.600

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.407 AC: 45019 AN: 110637 Hom.: 7307 Cov.: 23 AF XY: 0.393 AC XY: 12944 AN XY: 32949

African (AFR) AF: 0.297 AC: 9018 AN: 30331

American (AMR) AF: 0.333 AC: 3484 AN: 10464

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1221 AN: 2616

East Asian (EAS) AF: 0.0181 AC: 64 AN: 3542

South Asian (SAS) AF: 0.181 AC: 482 AN: 2661

European-Finnish (FIN) AF: 0.395 AC: 2313 AN: 5852

Middle Eastern (MID) AF: 0.584 AC: 125 AN: 214

European-Non Finnish (NFE) AF: 0.518 AC: 27347 AN: 52777

Other (OTH) AF: 0.426 AC: 643 AN: 1509

Alfa AF: 0.466 Hom.: 46498

Bravo AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.78
DANN	Benign	0.64
PhyloP100		-0.0070
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs530501; hg19: chrX-148567451;