U.S. flag

An official website of the United States government

NM_000824.5(GLRB):c.123-2A>G AND Hyperekplexia 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 15, 2018
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:
RCV000696345.8

Allele description [Variation Report for NM_000824.5(GLRB):c.123-2A>G]

NM_000824.5(GLRB):c.123-2A>G

Gene:
GLRB:glycine receptor beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q32.1
Genomic location:
Preferred name:
NM_000824.5(GLRB):c.123-2A>G
HGVS:
  • NC_000004.12:g.157120554A>G
  • NG_015823.1:g.49430A>G
  • NG_015823.2:g.49406A>G
  • NM_000824.5:c.123-2A>GMANE SELECT
  • NM_001166060.2:c.123-2A>G
  • NM_001166061.2:c.123-2A>G
  • NC_000004.11:g.158041706A>G
  • NM_000824.4:c.123-2A>G
Links:
dbSNP: rs1415892964
NCBI 1000 Genomes Browser:
rs1415892964
Molecular consequence:
  • NM_000824.5:c.123-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001166060.2:c.123-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001166061.2:c.123-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Hyperekplexia 2 (HKPX2)
Identifiers:
MONDO: MONDO:0013828; MedGen: C3553291; Orphanet: 3197; OMIM: 614619

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000824902Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 15, 2018) 		germlineclinical testing

PubMed (3)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

GLRB is the third major gene of effect in hyperekplexia.

Chung SK, Bode A, Cushion TD, Thomas RH, Hunt C, Wood SE, Pickrell WO, Drew CJ, Yamashita S, Shiang R, Leiz S, Longardt AC, Raile V, Weschke B, Puri RD, Verma IC, Harvey RJ, Ratnasinghe DD, Parker M, Rittey C, Masri A, Lingappa L, et al.

Hum Mol Genet. 2013 Mar 1;22(5):927-40. doi: 10.1093/hmg/dds498. Epub 2012 Nov 25. Erratum in: Hum Mol Genet. 2013 Jun 15;22(12):2552. Longhardt, Ann-Carolyn [corrected to Longardt, Ann-Carolyn].

PubMed [citation]
PMID:
23184146
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000824902.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change affects an acceptor splice site in intron 2 of the GLRB 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 occurs with a pathogenic variant (p.Ser150Lysfs*6) in GLRB in an individual with GLRB-related disease (Invitae). Family studies indicate these two variants are on opposite chromosomes (in trans), which suggests the c.123-2A>G substitution may contribute to disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GLRB are known to be pathogenic (PMID: 23184146). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024