chr4-1002713-G-GCCCCCCC

Variant names:

• chr4-1002713-G-GCCCCCCC
• rs150523349
• NM_000203.5:c.1190-16_1190-10dupCCCCCCC

Variant summary

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

The NM_000203.5(IDUA):​c.1190-16_1190-10dupCCCCCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000823 in 1,214,900 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: not found (cov: 29)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: IDUA NM_000203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 0 publications found

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

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000203.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDUA	NM_000203.5	MANE Select	c.1190-16_1190-10dupCCCCCCC		intron	N/A	NP_000194.2
	IDUA	NM_001363576.1		c.794-16_794-10dupCCCCCCC		intron	N/A	NP_001350505.1
	IDUA	NR_110313.1		n.1278-16_1278-10dupCCCCCCC		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDUA	ENST00000514224.2	TSL:2 MANE Select	c.1190-16_1190-10dupCCCCCCC		intron	N/A	ENSP00000425081.2
	IDUA	ENST00000247933.9	TSL:1	c.1190-16_1190-10dupCCCCCCC		intron	N/A	ENSP00000247933.4
	IDUA	ENST00000514698.5	TSL:5	n.1297-16_1297-10dupCCCCCCC		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 8.23e-7 AC: 1 AN: 1214900 Hom.: 0 Cov.: 24 AF XY: 0.00000166 AC XY: 1 AN XY: 601844

African (AFR) AF: 0.00 AC: 0 AN: 24134

American (AMR) AF: 0.00 AC: 0 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: 0.0000148 AC: 1 AN: 67648

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: 0.00 AC: 0 AN: 955414

Other (OTH) AF: 0.00 AC: 0 AN: 50974

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.79

Splicing

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

Other links and lift over

dbSNP: rs150523349; hg19: chr4-996501;