VCV000134207.19 - ClinVar

NM_207122.2(EXT2):c.124A>G (p.Met42Val)

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.

(8)

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_207122.2(EXT2):c.124A>G (p.Met42Val)

Variation ID: 134207 Accession: VCV000134207.19

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p11.2 11: 44107836 (GRCh38) [ NCBI UCSC ] 11: 44129386 (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	Jun 9, 2014	Sep 29, 2024	Jan 28, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_207122.2:c.124A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_997005.1:p.Met42Val	missense
NM_000401.3:c.223A>G	NP_000392.3:p.Met75Val	missense
NM_001178083.3:c.124A>G	NP_001171554.1:p.Met42Val	missense
NM_001389628.1:c.124A>G	NP_001376557.1:p.Met42Val	missense
NM_001389630.1:c.124A>G	NP_001376559.1:p.Met42Val	missense
NC_000011.10:g.44107836A>G
NC_000011.9:g.44129386A>G
NG_007560.1:g.17288A>G
LRG_494:g.17288A>G
LRG_494t1:c.223A>G	LRG_494p1:p.Met75Val
LRG_494t2:c.124A>G	LRG_494p2:p.Met42Val
	Q93063:p.Met42Val

... more HGVS ... less HGVS

Protein change

M42V, M75V

Other names

Canonical SPDI

NC_000011.10:44107835:A:G

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.

0.01298 (G)

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

The Genome Aggregation Database (gnomAD), exomes 0.00342

Exome Aggregation Consortium (ExAC) 0.00423

1000 Genomes Project 0.01298

The Genome Aggregation Database (gnomAD) 0.01478

1000 Genomes Project 30x 0.01515

Trans-Omics for Precision Medicine (TOPMed) 0.01561

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01661

Links

ClinGen: CA159126 UniProtKB: Q93063#VAR_033921 dbSNP: rs4755779 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.
EXT2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	771	874

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 (2)	criteria provided, single submitter	-	RCV000120880.6
not provided	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Oct 21, 2020	RCV000514384.7
Exostoses, multiple, type 2	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jan 28, 2024	RCV001086119.12
Exostoses, multiple, type 1	Benign (1)	criteria provided, single submitter	Jul 7, 2023	RCV003315753.1

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.
Likely benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Exostoses, multiple, type 2 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000371826.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Publications: PubMed (1) PubMed: 23262345 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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Benign (Oct 21, 2020)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001884320.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021
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: SCV000317229.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (May 04, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics Accession: SCV000609632.1 First in ClinVar: Nov 05, 2017 Last updated: Nov 05, 2017
Benign (Jan 28, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Exostoses, multiple, type 2 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001001047.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024
Benign (Jul 07, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Exostoses, multiple, type 1 Affected status: yes Allele origin: germline	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV004017520.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023
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: SCV005224220.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
not provided (Sep 19, 2013)	no classification provided Method: reference population	AllHighlyPenetrant Affected status: unknown Allele origin: germline	ITMI Accession: SCV000085048.1 First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 Comment: Please see associated publication for description of ethnicities	Publications: PubMed (1) PubMed: 24728327 Observation 1: Ethnicity/Population group: Whole_cohort Observation 2: Ethnicity/Population group: African Observation 3: Ethnicity/Population group: African_European Observation 4: Ethnicity/Population group: Central_Asian Observation 5: Ethnicity/Population group: East_Asian Observation 6: Ethnicity/Population group: European Observation 7: Ethnicity/Population group: Hispanic

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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely 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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
20 novel point mutations and one large deletion in EXT1 and EXT2 genes: report of diagnostic screening in a large Italian cohort of patients affected by hereditary multiple exostosis.	Ciavarella M	Gene	2013	PMID: 23262345

Text-mined citations for rs4755779 ...

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 Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_207122.2(EXT2):c.124A>G (p.Met42Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs4755779 ...