VCV000011029.1 - ClinVar

NCBI36/hg18 Xp22.13(chrX:17104696-17800261)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

NCBI36/hg18 Xp22.13(chrX:17104696-17800261)x3

Variation ID: 11029 Accession: VCV000011029.1

Type and length

copy number gain, -

Location

Cytogenetic: Xp22.13 -

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	Jul 25, 2013	Jul 25, 2013	Jul 15, 2009

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

OMIM: 300457.0007

Comment on variant

NCBI staff provided a description of the triplicated portion of this complex copy number gain based on the locations of breakpoints 2 and 3 cited in the paper by Coccia et al., 2009 (PubMed 19414485).

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.
NHS		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	543	729

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.
Cataract 40	Pathogenic (1)	no assertion criteria provided	Jul 15, 2009	RCV000011776.7

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 (Jul 15, 2009)	no assertion criteria provided Method: literature only	CATARACT 40 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000032008.2 First in ClinVar: Apr 04, 2013 Last updated: Jul 25, 2013	Publications: PubMed (3) PubMed: 11836358‚ 15370543‚ 19414485 Comment on evidence: In a 4-generation family with isolated X-linked congenital cataract (CTRCT40; 302200), originally described by Francis et al. (2002) and negative for mutation in the NHS … (more) In a 4-generation family with isolated X-linked congenital cataract (CTRCT40; 302200), originally described by Francis et al. (2002) and negative for mutation in the NHS gene (see Brooks et al., 2004), Coccia et al. (2009) performed array-comparative genomic hybridization (CGH) analysis and found a complex rearrangement consisting of a 500-kb triplication of a region encompassing the NHS, SCML1 (300227), and RAI2 (300217) genes embedded within a duplicated region (0.2 Mb distal and 0.1 Mb proximal to the embedded triplication). Further analysis revealed that 1 copy of the NHS gene lacked exon 1, another copy had all known exons but was disrupted upstream, and a third copy was intact; the 3 copies of the SCML1 and RAI2 genes appeared to be intact. The rearrangement segregated with disease in the family. The 500-kb triplication was predicted to result in altered transcriptional regulation of the NHS gene. (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
X-linked cataract and Nance-Horan syndrome are allelic disorders.	Coccia M	Human molecular genetics	2009	PMID: 19414485
Refinement of the X-linked cataract locus (CXN) and gene analysis for CXN and Nance-Horan syndrome (NHS).	Brooks S	Ophthalmic genetics	2004	PMID: 15370543
A locus for isolated cataract on human Xp.	Francis PJ	Journal of medical genetics	2002	PMID: 11836358

Text-mined citations for this variant ...

Record last updated May 08, 2024

ClinVar Genomic variation as it relates to human health

NCBI36/hg18 Xp22.13(chrX:17104696-17800261)x3

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...