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NM_000171.4(GLRA1):c.1059+1G>A AND Hereditary hyperekplexia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 21, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003762365.1

Allele description [Variation Report for NM_000171.4(GLRA1):c.1059+1G>A]

NM_000171.4(GLRA1):c.1059+1G>A

Gene:
GLRA1:glycine receptor alpha 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q33.1
Genomic location:
Preferred name:
NM_000171.4(GLRA1):c.1059+1G>A
HGVS:
  • NC_000005.10:g.151828920C>T
  • NG_011764.1:g.100917G>A
  • NM_000171.4:c.1059+1G>AMANE SELECT
  • NM_001146040.2:c.1059+1G>A
  • NM_001292000.2:c.810+1G>A
  • NC_000005.9:g.151208481C>T
Molecular consequence:
  • NM_000171.4:c.1059+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001146040.2:c.1059+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001292000.2:c.810+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Hereditary hyperekplexia
Synonyms:
Hyperexplexia, hereditary
Identifiers:
MONDO: MONDO:0021022; MedGen: C1835614; OMIM: PS149400

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004397008Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 21, 2023) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Hyperekplexia phenotype due to compound heterozygosity for GLRA1 gene mutations.

Vergouwe MN, Tijssen MA, Peters AC, Wielaard R, Frants RR.

Ann Neurol. 1999 Oct;46(4):634-8.

PubMed [citation]
PMID:
10514101

Functional characterization of compound heterozygosity for GlyRalpha1 mutations in the startle disease hyperekplexia.

Rea R, Tijssen MA, Herd C, Frants RR, Kullmann DM.

Eur J Neurosci. 2002 Jul;16(2):186-96.

PubMed [citation]
PMID:
12169101
See all PubMed Citations (8)

Details of each submission

From Invitae, SCV004397008.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 8 of the GLRA1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant has not been reported in the literature in individuals affected with GLRA1-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GLRA1 protein in which other variant(s) (p.Arg420His) have been determined to be pathogenic (PMID: 10514101, 12169101, 19732286, 20631190, 25036534; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 28, 2024