VCV000129165.31 - ClinVar

NM_004287.5(GOSR2):c.200G>A (p.Arg67Lys)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(15)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004287.5(GOSR2):c.200G>A (p.Arg67Lys)

Variation ID: 129165 Accession: VCV000129165.31

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.32 17: 46931204 (GRCh38) [ NCBI UCSC ] 17: 45008570 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 6, 2014	Sep 29, 2024	Jul 15, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_004287.5:c.200G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004278.2:p.Arg67Lys	missense
NM_001012511.3:c.200G>A	NP_001012529.1:p.Arg67Lys	missense
NM_001321133.2:c.200G>A	NP_001308062.1:p.Arg67Lys	missense
NM_001321134.2:c.146G>A	NP_001308063.1:p.Arg49Lys	missense
NM_001330252.2:c.200G>A	NP_001317181.1:p.Arg67Lys	missense
NM_001353114.2:c.197G>A	NP_001340043.1:p.Arg66Lys	missense
NM_001353115.2:c.197G>A	NP_001340044.1:p.Arg66Lys	missense
NM_001353116.2:c.197G>A	NP_001340045.1:p.Arg66Lys	missense
NM_001363851.2:c.146G>A	NP_001350780.1:p.Arg49Lys	missense
NM_054022.4:c.200G>A	NP_473363.1:p.Arg67Lys	missense
NR_148349.2:n.233G>A		non-coding transcript variant
NR_148350.2:n.233G>A		non-coding transcript variant
NR_148351.2:n.233G>A		non-coding transcript variant
NC_000017.11:g.46931204G>A
NC_000017.10:g.45008570G>A
NG_031806.2:g.13085G>A
	O14653:p.Arg67Lys

... more HGVS ... less HGVS

Protein change

R67K, R66K, R49K

Other names

Canonical SPDI

NC_000017.11:46931203:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.34605 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.31982

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.32477

The Genome Aggregation Database (gnomAD) 0.32616

1000 Genomes Project 30x 0.34416

The Genome Aggregation Database (gnomAD), exomes 0.34594

1000 Genomes Project 0.34605

Exome Aggregation Consortium (ExAC) 0.35101

Links

dbSNP: rs197922 ClinGen: CA152997 UniProtKB: O14653#VAR_024471 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
GOSR2		-	-	GRCh38 GRCh37	3	342
LOC126862578	-	-	-	GRCh38	-	90
LRRC37A2		-	-	GRCh38 GRCh38 GRCh38 GRCh37	-	645

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (7)	criteria provided, multiple submitters, no conflicts	Jul 15, 2024	RCV000117154.28
Progressive myoclonic epilepsy	Benign (2)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV000276471.20
not provided	Benign (3)	criteria provided, multiple submitters, no conflicts	Apr 20, 2017	RCV000711830.13
Myoclonic epilepsy, progressive, X-linked	Benign (1)	criteria provided, single submitter	May 28, 2019	RCV000989942.9
Progressive myoclonic epilepsy type 6	Benign (1)	criteria provided, single submitter	Aug 10, 2021	RCV001701753.10
Inborn genetic diseases	Benign (1)	criteria provided, single submitter	Jan 8, 2016	RCV002312117.9

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000310062.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Progressive Myoclonic Epilepsy Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000403687.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016	Publications: PubMed (2) PubMed: 19057520‚ 23449775
Benign (Apr 20, 2017)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV000842235.1 First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018
Benign (Jul 09, 2014)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000229032.5 First in ClinVar: Jun 28, 2015 Last updated: May 03, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GOSR2 Number of individuals with the variant: 1 Sex: mixed
Benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Myoclonic epilepsy, progressive, X-linked Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001140683.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Benign (Mar 03, 2015)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001897741.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021	Comment: This variant is associated with the following publications: (PMID: 19057520)
Benign (Aug 10, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Progressive myoclonic epilepsy type 6 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001933883.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Progressive myoclonic epilepsy Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001721732.4 First in ClinVar: Jun 15, 2021 Last updated: Feb 14, 2024
Benign (Jul 15, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: no Allele origin: germline	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan Accession: SCV005087629.1 First in ClinVar: Jul 23, 2024 Last updated: Jul 23, 2024	Comment: This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied in a panel designed for … (more) This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 47. Only high quality variants are reported. (less) Number of individuals with the variant: 47 Age: <18 years Sex: mixed
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005249301.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (Jan 08, 2016)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000845983.4 First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Likely benign (-)	no assertion criteria provided Method: clinical testing	AllHighlyPenetrant (Autosomal recessive inheritance) Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000151318.2 First in ClinVar: May 17, 2014 Last updated: Jul 06, 2014	Comment: Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more) Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. (less)
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001931996.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001959379.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001973362.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
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Comment:

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 47. Only high quality variants are reported.

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
'North Sea' progressive myoclonus epilepsy: phenotype of subjects with GOSR2 mutation.	Boissé Lomax L	Brain : a journal of neurology	2013	PMID: 23449775
GOSR2 Lys67Arg is associated with hypertension in whites.	Meyer TE	American journal of hypertension	2009	PMID: 19057520
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GOSR2	-	-	-	-

Text-mined citations for rs197922 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_004287.5(GOSR2):c.200G>A (p.Arg67Lys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs197922 ...