VCV002684642.1 - ClinVar

GRCh37/hg19 2q12.2-13(chr2:107029681-113127751)x1

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.

(1)

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.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

GRCh37/hg19 2q12.2-13(chr2:107029681-113127751)x1

Variation ID: 2684642 Accession: VCV002684642.1

Type and length

copy number loss, -

Location

Cytogenetic: 2q12.2-13 2: 107029681-113127751 (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	Jan 26, 2024	Jan 26, 2024	Jun 6, 2023

HGVS

Protein change

Other names

Canonical SPDI

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.

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

Links

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.
BCL2L11		No evidence available	No evidence available	GRCh38 GRCh37	22	85
ACOXL	-	-	-	GRCh38 GRCh37	50	120
ANAPC1		-	-	GRCh38 GRCh37	149	227
BUB1		-	-	GRCh38 GRCh37	1404	1464
CCDC138	-	-	-	GRCh38 GRCh37	-	113
EDAR		-	-	GRCh38 GRCh37	3	400
FBLN7		-	-	GRCh38 GRCh37	48	123
GCC2		-	-	GRCh38 GRCh37	141	188
LIMS1		-	-	GRCh38 GRCh37	35	84
LIMS3	-	-	-	GRCh38 GRCh37	-	33

There are 20 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh37) and ClinGen Dosage Sensitivity Map.

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 provided	Pathogenic (1)	criteria provided, single submitter	Jun 6, 2023	RCV003484838.1

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.
Pathogenic (Jun 06, 2023)	criteria provided, single submitter (ACMG/ClinGen CNV Guidelines, 2019) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV004230699.1 First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024	Comment: The copy number loss of 2q12.2q13 involves several protein-coding genes. This interval overlaps the recurrent 2q13 deletion syndrome region, which has been associated with variable … (more) The copy number loss of 2q12.2q13 involves several protein-coding genes. This interval overlaps the recurrent 2q13 deletion syndrome region, which has been associated with variable phenotypes (Wolfe 2018, Riley 2015, Hladilkova 2015, Yu 2012, Cooper 2011, Russell 2014, Digilio 2022), and has been shown to be significantly enriched in the clinical population (Coe 2014). Smaller deletions within the more proximal portion of this interval have been reported in individuals with additional features (Dittwald 2013, Huynh 2021, Khan 2018, Liu 2019, Coe 2014). Heterozygous frameshift sequence variants in RANBP2 and SH3RF3 have been identified in individuals with neurological disorders (Ganapathy 2019, Kosmicki 2017, Wang 2016). There are no similar copy number losses spanning this region in the general populations of the Database of Genomic Variants (DGV). Thus, based on gene content and current medical literature, this copy number variant (CNV) is classified as pathogenic. References: _x000D__x000D_ Coe et al., Nat Genet. 2014 Oct;46(10):1063-71. PMID: 25217958 _x000D__x000D_ Cooper et al., Nat Genet. 2011 Aug 14;43(9):838-46. PMID: 21841781 _x000D__x000D_ Digilio et al., Eur J Med Genet. 2022 Jan;65(1):104381. PMID: 34763108 _x000D__x000D_ Dittwald et al., Genome Res. 2013 Sep;23(9):1395-409. PMID: 23657883 _x000D__x000D_ Ganapathy et al., J Neurol. 2019 Aug;266(8):1919-1926. PMID: 31069529 _x000D__x000D_ Hladilkova et al., Mol Cytogenet. 2015 Jul 31;8:57. PMID: 26236398 _x000D__x000D_ Huynh et al., Neurogenetics. 2021 Jul;22(3):195-206. PMID: 34132911 _x000D__x000D_ Khan et al., Schizophr Res. 2018 Jul;197:337-345. PMID: 29486958 _x000D__x000D_ Kosmicki et al., Nat Genet. 2017 Apr;49(4):504-510. PMID: 28191890 _x000D__x000D_ Liu et al., Front Genet. 2019 Sep 10;10:819. PMID: 31552105 _x000D__x000D_ Riley et al., Am J Med Genet A. 2015 Nov;167A(11):2664-73. PMID: 26227573 _x000D__x000D_ Russell et al., Hum Mol Genet. 2014 Aug 15;23(16):4272-84. PMID: 24694933 _x000D__x000D_ Wang et al., Nat Commun. 2016 Nov 8;7:13316. PMID: 27824329 _x000D__x000D_ Wolfe et al., Am J Med Genet B Neuropsychiatr Genet. 2018 Jun;177(4):397-405. PMID: 29603867 _x000D__x000D_ Yu et al., Clin Genet. 2012 Mar;81(3):257-64. PMID: 21255006 (less)

Comment:

The copy number loss of 2q12.2q13 involves several protein-coding genes. This interval overlaps the recurrent 2q13 deletion syndrome region, which has been associated with variable phenotypes (Wolfe 2018, Riley 2015, Hladilkova 2015, Yu 2012, Cooper 2011, Russell 2014, Digilio 2022), and has been shown to be significantly enriched in the clinical population (Coe 2014). Smaller deletions within the more proximal portion of this interval have been reported in individuals with additional features (Dittwald 2013, Huynh 2021, Khan 2018, Liu 2019, Coe 2014). Heterozygous frameshift sequence variants in RANBP2 and SH3RF3 have been identified in individuals with neurological disorders (Ganapathy 2019, Kosmicki 2017, Wang 2016). There are no similar copy number losses spanning this region in the general populations of the Database of Genomic Variants (DGV). Thus, based on gene content and current medical literature, this copy number variant (CNV) is classified as pathogenic. References: _x000D__x000D_ Coe et al., Nat Genet. 2014 Oct;46(10):1063-71. PMID: 25217958 _x000D__x000D_ Cooper et al., Nat Genet. 2011 Aug 14;43(9):838-46. PMID: 21841781 _x000D__x000D_ Digilio et al., Eur J Med Genet. 2022 Jan;65(1):104381. PMID: 34763108 _x000D__x000D_ Dittwald et al., Genome Res. 2013 Sep;23(9):1395-409. PMID: 23657883 _x000D__x000D_ Ganapathy et al., J Neurol. 2019 Aug;266(8):1919-1926. PMID: 31069529 _x000D__x000D_ Hladilkova et al., Mol Cytogenet. 2015 Jul 31;8:57. PMID: 26236398 _x000D__x000D_ Huynh et al., Neurogenetics. 2021 Jul;22(3):195-206. PMID: 34132911 _x000D__x000D_ Khan et al., Schizophr Res. 2018 Jul;197:337-345. PMID: 29486958 _x000D__x000D_ Kosmicki et al., Nat Genet. 2017 Apr;49(4):504-510. PMID: 28191890 _x000D__x000D_ Liu et al., Front Genet. 2019 Sep 10;10:819. PMID: 31552105 _x000D__x000D_ Riley et al., Am J Med Genet A. 2015 Nov;167A(11):2664-73. PMID: 26227573 _x000D__x000D_ Russell et al., Hum Mol Genet. 2014 Aug 15;23(16):4272-84. PMID: 24694933 _x000D__x000D_ Wang et al., Nat Commun. 2016 Nov 8;7:13316. PMID: 27824329 _x000D__x000D_ Wolfe et al., Am J Med Genet B Neuropsychiatr Genet. 2018 Jun;177(4):397-405. PMID: 29603867 _x000D__x000D_ Yu et al., Clin Genet. 2012 Mar;81(3):257-64. PMID: 21255006

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 this variant ...

Record last updated Feb 04, 2024

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 2q12.2-13(chr2:107029681-113127751)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...