NM_000171.4(GLRA1):c.698-2del AND Hyperekplexia 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 25, 2019
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:: RCV001245198.1

Allele description [Variation Report for NM_000171.4(GLRA1):c.698-2del]

NM_000171.4(GLRA1):c.698-2del

Gene:

GLRA1:glycine receptor alpha 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q33.1

Genomic location:

Preferred name:

NM_000171.4(GLRA1):c.698-2del

HGVS:

NC_000005.10:g.151851606del
NG_011764.1:g.78231del
NM_000171.4:c.698-2delMANE SELECT
NM_001146040.2:c.698-2del
NM_001292000.2:c.449-2del
NC_000005.9:g.151231167del
NM_000171.3:c.698-2del

Links:

dbSNP: rs1752914673

NCBI 1000 Genomes Browser:

rs1752914673

Molecular consequence:

NM_000171.4:c.698-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001146040.2:c.698-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001292000.2:c.449-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Hyperekplexia 1 (STHE)
Synonyms:: Startle disease, familial; Startle reaction, exaggerated; Stiff-baby syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007868; MedGen: C4551954; Orphanet: 3197; OMIM: 149400

Recent activity

Clear Turn Off Turn On

Q3S4BO (0)
Protein
RecName: Full=Complement C4-A; AltName: Full=Acidic complement C4; AltName: Full...
RecName: Full=Complement C4-A; AltName: Full=Acidic complement C4; AltName: Full=C3 and PZP-like alpha-2-macroglobulin domain-containing protein 2; Contains: RecName: Full=Complement C4 beta chain; Contains: RecName: Full=Complement C4-A alpha chain; Contains: RecName: Full=C4a anaphylatoxin; Contains: RecName: Full=C4b-A; Contains: RecName: Full=C4d-A; Contains: RecName: Full=Complement C4 gamma chain; Flags: Precursor
gi|476007827|sp|P0C0L4.2|CO4A_HUMAN

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001418469	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 25, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20631190, 24108130, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001418469

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 25, 2019)

germline

clinical testing

PubMed (3)
[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

Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia.

Chung SK, Vanbellinghen JF, Mullins JG, Robinson A, Hantke J, Hammond CL, Gilbert DF, Freilinger M, Ryan M, Kruer MC, Masri A, Gurses C, Ferrie C, Harvey K, Shiang R, Christodoulou J, Andermann F, Andermann E, Thomas RH, Harvey RJ, Lynch JW, Rees MI.

J Neurosci. 2010 Jul 14;30(28):9612-20. doi: 10.1523/JNEUROSCI.1763-10.2010.

PubMed [citation]

PMID:: 20631190
PMCID:: PMC6632444

New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms.

Bode A, Wood SE, Mullins JGL, Keramidas A, Cushion TD, Thomas RH, Pickrell WO, Drew CJG, Masri A, Jones EA, Vassallo G, Born AP, Alehan F, Aharoni S, Bannasch G, Bartsch M, Kara B, Krause A, Karam EG, Matta S, Jain V, Mandel H, et al.

J Biol Chem. 2013 Nov 22;288(47):33745-33759. doi: 10.1074/jbc.M113.509240. Epub 2013 Oct 9.

PubMed [citation]

PMID:: 24108130
PMCID:: PMC3837119

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001418469.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change affects an acceptor splice site in intron 6 of the GLRA1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GLRA1-related conditions. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GLRA1 are known to be pathogenic (PMID: 20631190, 24108130). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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: Aug 5, 2023

ClinVar

Relating variation to medicine