Variant rs121965028 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting

The NM_000203.5(IDUA):c.1960_1962del(p.Ter654delextTer?) variant causes a stop lost, inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P653P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

IDUA
NM_000203.5 stop_lost, inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.82

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_000203.5. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDUA	NM_000203.5 linkuse as main transcript	c.1960_1962del	p.Ter654delextTer?	stop_lost, inframe_deletion	14/14	ENST00000514224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDUA	ENST00000514224.2 linkuse as main transcript	c.1960_1962del	p.Ter654delextTer?	stop_lost, inframe_deletion	14/14	2	NM_000203.5	P1	P35475-1
IDUA	ENST00000247933.9 linkuse as main transcript	c.1960_1962del	p.Ter654delextTer?	stop_lost, inframe_deletion	14/14	1		P1	P35475-1
IDUA	ENST00000514698.5 linkuse as main transcript	n.2071_2073del		non_coding_transcript_exon_variant	11/11	5
IDUA	ENST00000652070.1 linkuse as main transcript	n.2016_2018del		non_coding_transcript_exon_variant	13/13

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing