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:: RCV003762365.2

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

Recent activity

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sugar transport protein MST4-like [Cucumis melo]
sugar transport protein MST4-like [Cucumis melo]
gi|2316548789|ref|XP_008465176.2|

Protein
RecName: Full=Benzene 1,2-dioxygenase subunit alpha; AltName: Full=Benzene 1,2-d...
RecName: Full=Benzene 1,2-dioxygenase subunit alpha; AltName: Full=Benzene 1,2-dioxygenase P1 subunit; AltName: Full=Toluene 2,3-dioxygenase subunit alpha
gi|166225908|sp|P0C618.1|BNZA_PSEPU

Protein
Lymphoma, Primary Cutaneous Anaplastic Large Cell
Lymphoma, Primary Cutaneous Anaplastic Large Cell
Anaplastic lymphoma of the skin which develops as a primary neoplasm expressing the CD30 ANTIGEN. It is characterized by solitary nodules or ulcerated tumors....<br/>Year introduced: 2008

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004397008	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 21, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 10514101, 12169101, 19732286, 20631190, 25036534, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004397008

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 21, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004397008.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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