Genetic Variant NM_000202.8:c.*223_*224dupTT (chrX-149482521-T-TAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000202.8(IDS):c.*223_*224dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000037 ( 0 hom., 0 hem., cov: 7)

Exomes 𝑓: 0.000029 ( 0 hom. 0 hem. )

Consequence

IDS
NM_000202.8 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.135

Publications

0 publications found

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]

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

IDS links:

ENSG00000241489 (HGNC:):

ENSG00000241489 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDS	NM_000202.8 link	c.223_224dupTT		3_prime_UTR_variant	Exon 9 of 9	ENST00000340855.11	NP_000193.1	P22304-1
IDS	NM_001166550.4 link	c.223_224dupTT		3_prime_UTR_variant	Exon 9 of 9		NP_001160022.1	P22304B4DGD7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IDS	ENST00000340855.11 link	c.223_224dupTT	3_prime_UTR_variant	Exon 9 of 9	1	NM_000202.8	ENSP00000339801.6	P22304-1
ENSG00000241489	ENST00000651111.1 link	c.223_224dupTT	3_prime_UTR_variant	Exon 14 of 14			ENSP00000498395.1	B3KWA1
ENSG00000241489	ENST00000422081.6 link	c.223_224dupTT	downstream_gene_variant		2		ENSP00000477056.1	B3KWA1

Frequencies

GnomAD3 genomes

AF:

0.0000372

AC:

AN:

107568

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000994

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

GnomAD4 exome

AF:

0.0000295

AC:

AN:

305529

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

88301

show subpopulations

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

African (AFR)

AF:

0.000111

AC:

AN:

9000

American (AMR)

AF:

0.00

AC:

AN:

11036

Ashkenazi Jewish (ASJ)

AF:

0.000118

AC:

AN:

8488

East Asian (EAS)

AF:

0.000106

AC:

AN:

18896

South Asian (SAS)

AF:

0.00

AC:

AN:

22363

European-Finnish (FIN)

AF:

0.0000551

AC:

AN:

18138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1207

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

198688

Other (OTH)

AF:

0.0000565

AC:

AN:

17713

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.242

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000372

AC:

AN:

107602

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

30610

show subpopulations

African (AFR)

AF:

0.000101

AC:

AN:

29582

American (AMR)

AF:

0.0000993

AC:

AN:

10073

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2567

East Asian (EAS)

AF:

0.00

AC:

AN:

3439

South Asian (SAS)

AF:

0.00

AC:

AN:

2554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5231

Middle Eastern (MID)

AF:

0.00

AC:

AN:

202

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51832

Other (OTH)

AF:

0.00

AC:

AN:

1460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

672

Bravo

AF:

0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.14

Splicing

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

Publications

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NM_000202.8:c.223_224dupTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over