VCV001341063.1 - ClinVar

GRCh37/hg19 2q22.2-23.3(chr2:142409401-152680804)x3

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

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

GRCh37/hg19 2q22.2-23.3(chr2:142409401-152680804)x3

Variation ID: 1341063 Accession: VCV001341063.1

Type and length

copy number gain, -

Location

Cytogenetic: 2q22.2-23.3 2: 142409401-152680804 (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 13, 2022	Feb 13, 2022	Feb 1, 2021

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.
MBD5		Sufficient evidence for dosage pathogenicity	Little evidence for dosage pathogenicity	GRCh38 GRCh37	1545	1623
ZEB2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1356	1426
ACVR2A		-	-	GRCh38 GRCh37	11	47
ARHGAP15		-	-	GRCh38 GRCh37	24	56
ARL5A		-	-	GRCh38 GRCh37	9	32
EPC2		-	-	GRCh38 GRCh37	39	70
GTDC1		-	-	GRCh38 GRCh37	18	57
KYNU		-	-	GRCh38 GRCh37	81	105
LRP1B		-	-	GRCh38 GRCh37	400	427
LYPD6		-	-	GRCh38 GRCh37	10	31

There are 9 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)	no assertion criteria provided	Feb 1, 2021	RCV001834428.1

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 (Feb 01, 2021)	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV002095639.1 First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022	Comment: The copy number gain of 2q22.2q23.3 involves 20 protein-coding genes including ZEB2 (OMIM 605802), MBD5 (OMIM 611472) and KIF5C (OMIM 604593). It is expected to … (more) The copy number gain of 2q22.2q23.3 involves 20 protein-coding genes including ZEB2 (OMIM 605802), MBD5 (OMIM 611472) and KIF5C (OMIM 604593). It is expected to cause phenotypic and/or developmental abnormalities. Duplications of variable size over this region, mostly de novo, have been reported. The common features include developmental delay, cognitive impairment, facial dysmorphism, seizures, multiple congenital anomalies and behavioral abnormalities. Chung et al., reported two patients with duplications of region 2q23.1-2q23.2 including both EPC2 and MBD5 presenting with developmental delay and autistic features (Chung et al., Eur J Hum Genet. 2012 Apr;20(4):398-403. PMID: 22085900). Smaller duplications involving only ZEB2 or MBD5 gene locus have also been reported. Particularly, in a case series study of patients carrying duplications or deletions of 2q22.2q23.3, Mullegama et al. suggested the smallest region of overlap involved a single MBD5 gene locus (Mullegama et al. Eur J Hum Genet. 2014 Jan;22(1):57-63. PMID: 23632792). A de novo duplication at 2q22.2 including ZEB2, ARHGAP15 and GTDC1, was also reported in a patient with conotruncal heart defects (Mak et al., NPJ Genom Med. 2016 Sep 14;1:16033. PMID: 29263819). (less)

Comment:

The copy number gain of 2q22.2q23.3 involves 20 protein-coding genes including ZEB2 (OMIM 605802), MBD5 (OMIM 611472) and KIF5C (OMIM 604593). It is expected to cause phenotypic and/or developmental abnormalities. Duplications of variable size over this region, mostly de novo, have been reported. The common features include developmental delay, cognitive impairment, facial dysmorphism, seizures, multiple congenital anomalies and behavioral abnormalities. Chung et al., reported two patients with duplications of region 2q23.1-2q23.2 including both EPC2 and MBD5 presenting with developmental delay and autistic features (Chung et al., Eur J Hum Genet. 2012 Apr;20(4):398-403. PMID: 22085900). Smaller duplications involving only ZEB2 or MBD5 gene locus have also been reported. Particularly, in a case series study of patients carrying duplications or deletions of 2q22.2q23.3, Mullegama et al. suggested the smallest region of overlap involved a single MBD5 gene locus (Mullegama et al. Eur J Hum Genet. 2014 Jan;22(1):57-63. PMID: 23632792). A de novo duplication at 2q22.2 including ZEB2, ARHGAP15 and GTDC1, was also reported in a patient with conotruncal heart defects (Mak et al., NPJ Genom Med. 2016 Sep 14;1:16033. PMID: 29263819).

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 Apr 25, 2022

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 2q22.2-23.3(chr2:142409401-152680804)x3

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...