VCV000997469.10 - ClinVar

NM_207122.2(EXT2):c.1685G>A (p.Arg562Gln)

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.

(3)

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.

Conflicting classifications of pathogenicity
Uncertain significance(2); Likely benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_207122.2(EXT2):c.1685G>A (p.Arg562Gln)

Variation ID: 997469 Accession: VCV000997469.10

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p11.2 11: 44232375 (GRCh38) [ NCBI UCSC ] 11: 44253925 (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	Feb 28, 2021	Feb 14, 2024	Feb 11, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_207122.2:c.1685G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_997005.1:p.Arg562Gln	missense
NM_000401.3:c.1784G>A	NP_000392.3:p.Arg595Gln	missense
NM_001178083.3:c.1715G>A	NP_001171554.1:p.Arg572Gln	missense
NC_000011.10:g.44232375G>A
NC_000011.9:g.44253925G>A
NG_007560.1:g.141827G>A
LRG_494:g.141827G>A
LRG_494t1:c.1784G>A	LRG_494p1:p.Arg595Gln
LRG_494t2:c.1685G>A

... more HGVS ... less HGVS

Protein change

R562Q, R572Q, R595Q

Other names

Canonical SPDI

NC_000011.10:44232374: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.

0.00080 (A)

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

The Genome Aggregation Database (gnomAD), exomes 0.00008

Exome Aggregation Consortium (ExAC) 0.00012

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015

Trans-Omics for Precision Medicine (TOPMed) 0.00020

1000 Genomes Project 30x 0.00062

1000 Genomes Project 0.00080

Links

dbSNP: rs140561784 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	766	869

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.
Exostoses, multiple, type 2	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	Feb 11, 2023	RCV001292629.9
EXT2-related disorder	Uncertain significance (1)	criteria provided, single submitter	Aug 29, 2022	RCV003416156.4

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.
Uncertain significance (Oct 12, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Exostoses, multiple, type 2 Affected status: yes Allele origin: maternal	Baylor Genetics Study: CSER-TexasKidsCanSeq Accession: SCV001481221.2 First in ClinVar: Feb 28, 2021 Last updated: Feb 28, 2021	Comment: This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Likely benign (Feb 11, 2023)	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: SCV001532572.4 First in ClinVar: Mar 22, 2021 Last updated: Feb 14, 2024
Uncertain significance (Aug 29, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	EXT2-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004115610.1 First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023	Comment: The EXT2 c.1685G>A variant is predicted to result in the amino acid substitution p.Arg562Gln. To our knowledge, this variant has not been reported in the … (more) The EXT2 c.1685G>A variant is predicted to result in the amino acid substitution p.Arg562Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.080% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-44253925-G-A), which is likely too common for an undocumented disease-causing variant. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)

Comment:

The EXT2 c.1685G>A variant is predicted to result in the amino acid substitution p.Arg562Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.080% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-44253925-G-A), which is likely too common for an undocumented disease-causing variant. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs140561784 ...

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.1685G>A (p.Arg562Gln)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs140561784 ...