NM_000824.5(GLRB):c.281_282delinsGC (p.Ile94Ser) AND Hyperekplexia 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 3, 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:: RCV002297465.4

Allele description [Variation Report for NM_000824.5(GLRB):c.281_282delinsGC (p.Ile94Ser)]

NM_000824.5(GLRB):c.281_282delinsGC (p.Ile94Ser)

Gene:

GLRB:glycine receptor beta [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

4q32.1

Genomic location:

Preferred name:

NM_000824.5(GLRB):c.281_282delinsGC (p.Ile94Ser)

HGVS:

NC_000004.12:g.157122381_157122382delinsGC
NG_015823.2:g.51233_51234delinsGC
NM_000824.5:c.281_282delinsGCMANE SELECT
NM_001166060.2:c.281_282delinsGC
NM_001166061.2:c.281_282delinsGC
NP_000815.1:p.Ile94Ser
NP_001159532.1:p.Ile94Ser
NP_001159533.1:p.Ile94Ser
NC_000004.11:g.158043533_158043534delinsGC
NG_015823.1:g.51257_51258delinsGC

Protein change:

I94S

Molecular consequence:

NM_000824.5:c.281_282delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001166060.2:c.281_282delinsGC - missense variant - [Sequence Ontology: SO:0001583]
NM_001166061.2:c.281_282delinsGC - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002592820	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 3, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002592820

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 3, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002592820.3

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

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 94 of the GLRB protein (p.Ile94Ser). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with GLRB-related conditions. ClinVar contains an entry for this variant (Variation ID: 1717245). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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