rs71753099

Variant names:

• chrX-149482521-TAA-T
• rs71753099
• NM_000202.8:c.*223_*224delTT

Your query was ambiguous. Multiple possible variants found:

• chrX-149482521-TAA-T
• chrX-149482521-TAA-TA
• chrX-149482521-TAA-TAAA
• chrX-149482521-TAA-TAAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000202.8(IDS):​c.*223_*224delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 413,170 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., 3 hem., cov: 7)
  • Exomes 𝑓: 0.00011 (0 hom. 6 hem.)
• Consequence: IDS NM_000202.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00013 (14/107567) while in subpopulation NFE AF = 0.000212 (11/51836). AF 95% confidence interval is 0.000118. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 7. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 3 XL,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDS	NM_000202.8	c.*223_*224delTT		3_prime_UTR_variant	Exon 9 of 9	ENST00000340855.11	NP_000193.1
IDS	NM_001166550.4	c.*223_*224delTT		3_prime_UTR_variant	Exon 9 of 9		NP_001160022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDS	ENST00000340855.11	c.*223_*224delTT		3_prime_UTR_variant	Exon 9 of 9	1	NM_000202.8	ENSP00000339801.6
ENSG00000241489	ENST00000651111.1	c.*223_*224delTT		3_prime_UTR_variant	Exon 14 of 14			ENSP00000498395.1
ENSG00000241489	ENST00000422081.6	c.*223_*224delTT		downstream_gene_variant		2		ENSP00000477056.1

Frequencies

GnomAD3 genomes AF: 0.000130 AC: 14 AN: 107567 Hom.: 0 Cov.: 7

Gnomad AFR AF: 0.000102

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: 0.000212

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000111 AC: 34 AN: 305603 Hom.: 0 AF XY: 0.0000679 AC XY: 6 AN XY: 88301

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 9027

American (AMR) AF: 0.00 AC: 0 AN: 11052

Ashkenazi Jewish (ASJ) AF: 0.000118 AC: 1 AN: 8497

East Asian (EAS) AF: 0.00 AC: 0 AN: 18917

South Asian (SAS) AF: 0.00 AC: 0 AN: 22381

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1207

European-Non Finnish (NFE) AF: 0.000156 AC: 31 AN: 198669

Other (OTH) AF: 0.000113 AC: 2 AN: 17721

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000130 AC: 14 AN: 107567 Hom.: 0 Cov.: 7 AF XY: 0.0000982 AC XY: 3 AN XY: 30563

African (AFR) AF: 0.000102 AC: 3 AN: 29527

American (AMR) AF: 0.00 AC: 0 AN: 10061

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2567

East Asian (EAS) AF: 0.00 AC: 0 AN: 3450

South Asian (SAS) AF: 0.00 AC: 0 AN: 2567

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5231

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 225

European-Non Finnish (NFE) AF: 0.000212 AC: 11 AN: 51836

Other (OTH) AF: 0.00 AC: 0 AN: 1441

Alfa AF: 0.00 Hom.: 672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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: rs71753099; hg19: chrX-148564052;