VCV000007099.67 - ClinVar

NM_001008212.2(OPTN):c.293T>A (p.Met98Lys)

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.

(16)

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/Likely 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_001008212.2(OPTN):c.293T>A (p.Met98Lys)

Variation ID: 7099 Accession: VCV000007099.67

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10p13 10: 13110400 (GRCh38) [ NCBI UCSC ] 10: 13152400 (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	Sep 18, 2016	Sep 29, 2024	Jan 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001008212.2:c.293T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001008213.1:p.Met98Lys	missense
NM_001008211.1:c.293T>A	NP_001008212.1:p.Met98Lys	missense
NM_001008213.1:c.293T>A	NP_001008214.1:p.Met98Lys	missense
NM_021980.4:c.293T>A	NP_068815.2:p.Met98Lys	missense
NC_000010.11:g.13110400T>A
NC_000010.10:g.13152400T>A
NG_012876.1:g.15319T>A
NG_051826.1:g.1956T>A

... more HGVS ... less HGVS

Protein change

M98K

Other names

Canonical SPDI

NC_000010.11:13110399:T: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.

0.07867 (A)

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

The Genome Aggregation Database (gnomAD), exomes 0.04422

Exome Aggregation Consortium (ExAC) 0.04519

The Genome Aggregation Database (gnomAD) 0.05969

Trans-Omics for Precision Medicine (TOPMed) 0.06176

1000 Genomes Project 0.07867

1000 Genomes Project 30x 0.07886

Links

ClinGen: CA118632 OMIM: 602432.0004 dbSNP: rs11258194 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.
LOC108903148	-	-	-	GRCh38	-	95
OPTN		-	-	GRCh38 GRCh37	382	513

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.
Glaucoma, normal tension, susceptibility to	risk factor (1)	no assertion criteria provided	Feb 8, 2002	RCV000007516.14
Glaucoma 1, open angle, E	Pathogenic (1)	no assertion criteria provided	Feb 8, 2002	RCV000007517.14
not specified	Benign (5)	criteria provided, multiple submitters, no conflicts	May 8, 2014	RCV000177328.23
Amyotrophic lateral sclerosis type 12	Benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000324769.14
Primary open angle glaucoma	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	May 28, 2019	RCV000269750.15
Amyotrophic lateral sclerosis type 12 Glaucoma 1, open angle, E Primary open angle glaucoma	Benign (1)	criteria provided, single submitter	Jan 31, 2024	RCV001512340.18
Amyotrophic lateral sclerosis type 12 Glaucoma, normal tension, susceptibility to Primary open angle glaucoma	Benign (1)	criteria provided, single submitter	Feb 25, 2022	RCV002490331.8
not provided	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Nov 29, 2023	RCV001705584.17

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: SCV000305653.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (May 08, 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: SCV000229175.5 First in ClinVar: Jun 28, 2015 Last updated: Oct 02, 2016	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=OPTN Number of individuals with the variant: 3 Sex: mixed
Likely benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Primary open angle glaucoma Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001137998.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Amyotrophic lateral sclerosis type 12 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000361403.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less)
Benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Primary open angle glaucoma Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000361402.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Publications: PubMed (5) PubMed: 15761120‚ 16619239‚ 11834836‚ 12208142‚ 11978762 Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
Benign (Nov 29, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000604575.6 First in ClinVar: Oct 02, 2016 Last updated: Feb 20, 2024
Benign (Sep 12, 2018)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001893088.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021	Comment: This variant is associated with the following publications: (PMID: 16358725, 17361544, 31198474, 31182772, 17293779, 28430856, 26376340, 25681989, 15226658, 11834836, 19172505, 17122126, 23357852)
Benign (Feb 25, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Primary open angle glaucoma Glaucoma, normal tension, susceptibility to Amyotrophic lateral sclerosis type 12 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002800205.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Primary open angle glaucoma Glaucoma 1, open angle, E Amyotrophic lateral sclerosis type 12 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001719737.5 First in ClinVar: Jun 15, 2021 Last updated: Feb 28, 2024
Likely 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: SCV005226930.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
risk factor (Feb 08, 2002)	no assertion criteria provided Method: literature only	GLAUCOMA, NORMAL TENSION, SUSCEPTIBILITY TO Affected status: not provided Allele origin: germline	OMIM Accession: SCV000027717.4 First in ClinVar: Apr 04, 2013 Last updated: Jan 09, 2021	Publications: PubMed (1) PubMed: 11834836 Comment on evidence: Within a group of 169 patients with autosomal dominant adult-onset open angle glaucoma (GLC1E; 137760), Rezaie et al. (2002) identified a 603T-A transversion in exon … (more) Within a group of 169 patients with autosomal dominant adult-onset open angle glaucoma (GLC1E; 137760), Rezaie et al. (2002) identified a 603T-A transversion in exon 5 of the OPTN gene, resulting in a met98-to-lys substitution in 8 of 45 familial (17.8%) and 15 of 124 (12.1%) sporadic individuals with glaucoma. Most of these individuals had normal intraocular pressure (606657) and were screened for sequence changes in exon 5 only. This mutation was also identified in 9 of 422 normal chromosomes, giving the overall identification in an at-risk population of 13.6% versus 2.1% in the general population, and making this a risk-associated alteration. (less)
Pathogenic (Feb 08, 2002)	no assertion criteria provided Method: literature only	GLAUCOMA 1, OPEN ANGLE, E Affected status: not provided Allele origin: germline	OMIM Accession: SCV000027718.4 First in ClinVar: Apr 04, 2013 Last updated: Jan 09, 2021	Publications: PubMed (1) PubMed: 11834836 Comment on evidence: Within a group of 169 patients with autosomal dominant adult-onset open angle glaucoma (GLC1E; 137760), Rezaie et al. (2002) identified a 603T-A transversion in exon … (more) Within a group of 169 patients with autosomal dominant adult-onset open angle glaucoma (GLC1E; 137760), Rezaie et al. (2002) identified a 603T-A transversion in exon 5 of the OPTN gene, resulting in a met98-to-lys substitution in 8 of 45 familial (17.8%) and 15 of 124 (12.1%) sporadic individuals with glaucoma. Most of these individuals had normal intraocular pressure (606657) and were screened for sequence changes in exon 5 only. This mutation was also identified in 9 of 422 normal chromosomes, giving the overall identification in an at-risk population of 13.6% versus 2.1% in the general population, and making this a risk-associated alteration. (less)
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, Amsterdam University Medical Center Study: VKGL Data-share Consensus Accession: SCV001808244.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001922414.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
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: SCV001929934.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 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: SCV001965788.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
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Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

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:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Long-range PCR facilitates the identification of PMS2-specific mutations.	Clendenning M	Human mutation	2006	PMID: 16619239
Complement factor H variant increases the risk of age-related macular degeneration.	Haines JL	Science (New York, N.Y.)	2005	PMID: 15761120
Structure of human succinic semialdehyde dehydrogenase gene: identification of promoter region and alternatively processed isoforms.	Blasi P	Molecular genetics and metabolism	2002	PMID: 12208142
VSX1: a gene for posterior polymorphous dystrophy and keratoconus.	Héon E	Human molecular genetics	2002	PMID: 11978762
Adult-onset primary open-angle glaucoma caused by mutations in optineurin.	Rezaie T	Science (New York, N.Y.)	2002	PMID: 11834836
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=OPTN	-	-	-	-

Text-mined citations for rs11258194 ...

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 10, 2024

ClinVar Genomic variation as it relates to human health

NM_001008212.2(OPTN):c.293T>A (p.Met98Lys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs11258194 ...