GeneBe

4-1002713-G-GCCC

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000203.5(IDUA):​c.1190-12_1190-10dupCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000513 in 1,364,560 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 29)
Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

IDUA
NM_000203.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.792

Publications

3 publications found
Variant links:
Genes affected
IDUA (HGNC:5391): (alpha-L-iduronidase) This gene encodes an enzyme that hydrolyzes the terminal alpha-L-iduronic acid residues of two glycosaminoglycans, dermatan sulfate and heparan sulfate. This hydrolysis is required for the lysosomal degradation of these glycosaminoglycans. Mutations in this gene that result in enzymatic deficiency lead to the autosomal recessive disease mucopolysaccharidosis type I (MPS I). [provided by RefSeq, Jul 2008]
IDUA Gene-Disease associations (from GenCC):
  • mucopolysaccharidosis type 1
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Myriad Women’s Health
  • Scheie syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Orphanet
  • Hurler syndrome
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia
  • Hurler-Scheie syndrome
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IDUANM_000203.5 linkc.1190-12_1190-10dupCCC intron_variant Intron 8 of 13 ENST00000514224.2 NP_000194.2
IDUANM_001363576.1 linkc.794-12_794-10dupCCC intron_variant Intron 7 of 12 NP_001350505.1
IDUANR_110313.1 linkn.1278-12_1278-10dupCCC intron_variant Intron 8 of 13
IDUAXM_047415650.1 linkc.1190-12_1190-10dupCCC intron_variant Intron 8 of 11 XP_047271606.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IDUAENST00000514224.2 linkc.1190-12_1190-10dupCCC intron_variant Intron 8 of 13 2 NM_000203.5 ENSP00000425081.2

Frequencies

GnomAD3 genomes
AF:
0.00000668
AC:
1
AN:
149678
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000149
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000137
AC:
1
AN:
73188
AF XY:
0.00
show subpopulations
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:
0.0000377
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000494
AC:
6
AN:
1214882
Hom.:
0
Cov.:
24
AF XY:
0.00000498
AC XY:
3
AN XY:
601828
show subpopulations
⚠️ 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:
24134
American (AMR)
AF:
0.0000344
AC:
1
AN:
29060
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22434
East Asian (EAS)
AF:
0.00
AC:
0
AN:
28878
South Asian (SAS)
AF:
0.0000591
AC:
4
AN:
67640
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
32742
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3616
European-Non Finnish (NFE)
AF:
0.00000105
AC:
1
AN:
955404
Other (OTH)
AF:
0.00
AC:
0
AN:
50974
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000011619), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.317
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000668
AC:
1
AN:
149678
Hom.:
0
Cov.:
29
AF XY:
0.0000137
AC XY:
1
AN XY:
72992
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
40604
American (AMR)
AF:
0.00
AC:
0
AN:
15138
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3442
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5046
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4726
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10262
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
306
European-Non Finnish (NFE)
AF:
0.0000149
AC:
1
AN:
67210
Other (OTH)
AF:
0.00
AC:
0
AN:
2046
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
-0.79

Splicing

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

Publications

Other links and lift over

dbSNP: rs150523349; hg19: chr4-996501; API