X-149482521-TA-T

Variant names:

• chrX-149482521-TA-T
• rs71753099
• NM_000202.8:c.*224delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000202.8(IDS):​c.*224delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (5392 hom., 10708 hem., cov: 7)
  • Exomes 𝑓: 0.37 (15497 hom. 28881 hem.)
• Consequence: IDS NM_000202.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.135
• 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 -10 ACMG points.

• BP6: Variant X-149482521-TA-T is Benign according to our data. Variant chrX-149482521-TA-T is described in ClinVar as [Benign]. Clinvar id is 1286955.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDS	NM_000202.8	c.*224delT		3_prime_UTR_variant	Exon 9 of 9	ENST00000340855.11	NP_000193.1
IDS	NM_001166550.4	c.*224delT		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.*224delT		3_prime_UTR_variant	Exon 9 of 9	1	NM_000202.8	ENSP00000339801.6
ENSG00000241489	ENST00000651111.1	c.*224delT		3_prime_UTR_variant	Exon 14 of 14			ENSP00000498395.1
ENSG00000241489	ENST00000422081.6	c.*224delT		downstream_gene_variant		2		ENSP00000477056.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 38475 AN: 107491 Hom.: 5394 Cov.: 7

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.498

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.373 AC: 112640 AN: 302191 Hom.: 15497 Cov.: 0 AF XY: 0.336 AC XY: 28881 AN XY: 86025

African (AFR) AF: 0.271 AC: 2425 AN: 8939

American (AMR) AF: 0.229 AC: 2500 AN: 10927

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 2911 AN: 8401

East Asian (EAS) AF: 0.135 AC: 2511 AN: 18653

South Asian (SAS) AF: 0.167 AC: 3686 AN: 22027

European-Finnish (FIN) AF: 0.420 AC: 7536 AN: 17943

Middle Eastern (MID) AF: 0.361 AC: 428 AN: 1186

European-Non Finnish (NFE) AF: 0.428 AC: 84127 AN: 196577

Other (OTH) AF: 0.372 AC: 6516 AN: 17538

GnomAD4 genome AF: 0.358 AC: 38466 AN: 107525 Hom.: 5392 Cov.: 7 AF XY: 0.350 AC XY: 10708 AN XY: 30569

African (AFR) AF: 0.271 AC: 8024 AN: 29562

American (AMR) AF: 0.267 AC: 2691 AN: 10065

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 928 AN: 2564

East Asian (EAS) AF: 0.140 AC: 482 AN: 3438

South Asian (SAS) AF: 0.155 AC: 395 AN: 2553

European-Finnish (FIN) AF: 0.450 AC: 2346 AN: 5217

Middle Eastern (MID) AF: 0.475 AC: 96 AN: 202

European-Non Finnish (NFE) AF: 0.438 AC: 22682 AN: 51802

Other (OTH) AF: 0.363 AC: 530 AN: 1460

Alfa AF: 0.162 Hom.: 672

Bravo AF: 0.340

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14
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: rs71753099; hg19: chrX-148564052; COSMIC: COSV61711589; COSMIC: COSV61711589;