U.S. flag

An official website of the United States government

NM_020988.3(GNAO1):c.736G>A (p.Glu246Lys) AND GNAO1-related developmental delay-seizures-movement disorder spectrum

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 10, 2020
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:
RCV003996903.1

Allele description [Variation Report for NM_020988.3(GNAO1):c.736G>A (p.Glu246Lys)]

NM_020988.3(GNAO1):c.736G>A (p.Glu246Lys)

Gene:
GNAO1:G protein subunit alpha o1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q13
Genomic location:
Preferred name:
NM_020988.3(GNAO1):c.736G>A (p.Glu246Lys)
HGVS:
  • NC_000016.10:g.56351396G>A
  • NG_042800.1:g.165058G>A
  • NM_020988.3:c.736G>AMANE SELECT
  • NP_066268.1:p.Glu246Lys
  • NC_000016.9:g.56385308G>A
  • NM_020988.2:c.736G>A
  • P09471:p.Glu246Lys
Protein change:
E246K; GLU246LYS
Links:
UniProtKB: P09471#VAR_077339; OMIM: 139311.0007; dbSNP: rs797044951
NCBI 1000 Genomes Browser:
rs797044951
Molecular consequence:
  • NM_020988.3:c.736G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
GNAO1-related developmental delay-seizures-movement disorder spectrum
Identifiers:
MONDO: MONDO:0035660; MedGen: C5680303

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
SCV004814153Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSLVariantClassificationCriteria RUGD 01 April 2020)		Pathogenic
(May 10, 2020) 		unknownclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From Illumina Laboratory Services, Illumina, SCV004814153.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The GNAO1 c.736G>A p.(Glu246Lys) missense variant has been identified in individuals with a phenotype consistent with GNAO1-related developmental delay-seizures-movement disorder spectrum. The variant occurred de novo in at least four of the individuals (Feng et al. 2018). This variant is not observed in version 2.1.1 of the Genome Aggregation Database. Functional studies found that when the p.Glu246Lys variant expressed in HEK293T cells, it exhibited increased potency for alpha-2A AR-mediated cAMP inhibition consistent with a gain-of-function mechanism (Feng et al. 2017). Multiple lines of computational evidence suggest the variant may impact the gene or gene product. The variant was identified in a de novo state in the proband. Based on the collective evidence the c.736G>A p.(Glu246Lys) variant is classified as pathogenic for GNAO1-related developmental delay-seizures-movement disorder spectrum.

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

Last Updated: Sep 29, 2024