VCV000988905.4 - ClinVar

GRCh37/hg19 10q11.22-11.23(chr10:49391938-51053159)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.

Uncertain significance

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

GRCh37/hg19 10q11.22-11.23(chr10:49391938-51053159)x3

Variation ID: 988905 Accession: VCV000988905.4

Type and length

copy number gain, 1,661,222 bp

Location

Cytogenetic: 10q11.22-11.23 10: 49391938-51053159 (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	Dec 19, 2020	Mar 4, 2023	Nov 11, 2020

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.
ARHGAP22		-	-	GRCh38 GRCh37	74	162
C10orf53	-	-	-	GRCh38 GRCh37	2	88
C10orf71	-	-	-	GRCh38 GRCh37	22	109
CHAT		-	-	GRCh38 GRCh37	971	1309
DRGX		-	-	GRCh38 GRCh37	1	88
ERCC6		-	-	GRCh38 GRCh37	1580	1957
FAM170B	-	-	-	GRCh38 GRCh37	-	119
FRMPD2		-	-	GRCh38 GRCh37	103	190
LRRC18		-	-	GRCh38 GRCh37	-	107
MAPK8		-	-	GRCh38 GRCh37	21	108

There are 7 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh37).

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	Uncertain significance (1)	criteria provided, single submitter	Nov 11, 2020	RCV001270635.4

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 (Nov 11, 2020)	criteria provided, single submitter (ICSL CNVClassificationCriteria Aug2020) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Illumina Laboratory Services, Illumina Accession: SCV001451366.2 First in ClinVar: Dec 19, 2020 Last updated: Mar 04, 2023	Publications: PubMed (2) PubMed: 21948486‚ 28846756 Comment: This CNV is an inherited 1.7 Mb duplication of 10q11.22-q11.23, on chromosome 10, (seq[GRCh37]dup(10)(q11.22q11.23); chr10:g.4931938_51053159dup) and constitutes a gain encompassing 18 protein coding genes. Two … (more) This CNV is an inherited 1.7 Mb duplication of 10q11.22-q11.23, on chromosome 10, (seq[GRCh37]dup(10)(q11.22q11.23); chr10:g.4931938_51053159dup) and constitutes a gain encompassing 18 protein coding genes. Two 18-year-old monozygotic twins with an overlapping de novo 1.7 Mb duplication presented with seizures, intellectual disability, autistic features, short stature, and microcephaly (Borlot et al. 2017). At least seven individuals are reported with similar sized gains in this region, four of which were inherited from an unaffected parent and three of which were with unknown inheritance (Stankiewicz et al. 2012). The phenotypes observed in these individuals ranged from autism, speech delay, developmental delay, dysmorphic features, seizures and skeletal anomalies. The region has been shown to contain several large, directly orientated segmental duplications of >98% sequence identity suggesting that non-allelic homologous recombination is the mechanism of genomic rearrangement in this region (Stankiewicz et al. 2012). This CNV has not been reported in controls. Based on the limited evidence, this CNV is classified as a variant of uncertain significance. (less)

Comment:

This CNV is an inherited 1.7 Mb duplication of 10q11.22-q11.23, on chromosome 10, (seq[GRCh37]dup(10)(q11.22q11.23); chr10:g.4931938_51053159dup) and constitutes a gain encompassing 18 protein coding genes. Two 18-year-old monozygotic twins with an overlapping de novo 1.7 Mb duplication presented with seizures, intellectual disability, autistic features, short stature, and microcephaly (Borlot et al. 2017). At least seven individuals are reported with similar sized gains in this region, four of which were inherited from an unaffected parent and three of which were with unknown inheritance (Stankiewicz et al. 2012). The phenotypes observed in these individuals ranged from autism, speech delay, developmental delay, dysmorphic features, seizures and skeletal anomalies. The region has been shown to contain several large, directly orientated segmental duplications of >98% sequence identity suggesting that non-allelic homologous recombination is the mechanism of genomic rearrangement in this region (Stankiewicz et al. 2012). This CNV has not been reported in controls. Based on the limited evidence, this CNV is classified as a variant of uncertain significance.

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
Prevalence of Pathogenic Copy Number Variation in Adults With Pediatric-Onset Epilepsy and Intellectual Disability.	Borlot F	JAMA neurology	2017	PMID: 28846756
Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-copy repeats.	Stankiewicz P	Human mutation	2012	PMID: 21948486

Text-mined citations for this variant ...

Record last updated Apr 09, 2023

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 10q11.22-11.23(chr10:49391938-51053159)x3

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...