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Intellectual disability

STR: GLS_GCA

Red List (low evidence)
Chromosome: 2
GRCh37 Position: 191745599-191745646
GRCh38 Position: 190880873-190880920
Repeated Sequence: GCA
Normal Number of Repeats: < 50
Pathogenic Number of Repeats: = or > 400

GLS (glutaminase)
EnsemblGeneIds (GRCh38): ENSG00000115419
EnsemblGeneIds (GRCh37): ENSG00000115419
OMIM: 138280, Gene2Phenotype
GLS is in 0 panels

1 review

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Early developmental delay, which preceded other progressive neurological concerns, was reported in the three unrelated cases from PMID:30970188. Following discussion with Helen Brittain (Genomics England Clinical Team) it was agreed that this is sufficient for inclusion on this panel.

However, detection of this 5' UTR triplet expansion must first be validated within the Genomics England pipeline. In the meantime, rating Red but will raise the STR for validation with the Rare Disease team.
Created: 18 Jan 2021, 7:38 p.m. | Last Modified: 19 Jan 2021, 10:13 a.m.
Panel Version: 3.714
- PMID: 30970188 (2019) - Three unrelated cases who presented with an early-onset global developmental delay, progressive ataxia, and elevated levels of glutamine. One patient also showed cerebellar atrophy.

All 3 individuals harboured a large trinucleotide (GCA) repeat expansion in the 5' UTR (length: 680-1,500-copy repeats). The repeat expansion was found in homozygosity in 1 case, and occurred in compound heterozygosity with an SNV in the other two cases (missense and frameshift variant, respectively). Functional analysis showed the repeat expansion results in reduced expression and glutaminase deficiency.
Sources: Literature
Created: 18 Jan 2021, 3:46 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733

Publications

Created: 18 Jan 2021, 3:46 p.m.
Last Modified: 19 Jan 2021, 10:13 a.m.
Panel version: 3.709

Details

Name
GLS_GCA
Chromosome
2
GRCh37 Coordinates
191745599-191745646
GRCh38 Coordinates
190880873-190880920
Repeated Sequence
GCA
Normal Number of Repeats: <
50
Pathogenic Number of Repeats: = or >
400
Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Literature
Phenotypes
  • Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412
Tags
STR NGS Not Validated
OMIM
138280
Clinvar variants
Variants in GLS
Penetrance
None
Publications

History Filter Activity

8 Jun 2022, Gel status: 1

Removed Tag

Eleanor Williams (Genomics England Curator)

Tag for-review was removed from STR: GLS_GCA.

11 Nov 2021, Gel status: 1

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for STR: GLS_GCA were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412

19 Jan 2021, Gel status: 1

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag NGS Not Validated tag was added to STR: GLS_GCA.

18 Jan 2021, Gel status: 1

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Str: gls_gca has been classified as Red List (Low Evidence).

18 Jan 2021, Gel status: 1

Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag STR tag was added to STR: GLS_GCA. Tag for-review tag was added to STR: GLS_GCA.

18 Jan 2021, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Arina Puzriakova (Genomics England Curator)

STR: GLS_GCA was added STR: GLS_GCA was added to Intellectual disability. Sources: Literature Mode of inheritance for STR: GLS_GCA was set to BIALLELIC, autosomal or pseudoautosomal Publications for STR: GLS_GCA were set to 30970188 Phenotypes for STR: GLS_GCA were set to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733 Review for STR: GLS_GCA was set to GREEN