VCV001809431.1 - ClinVar

GRCh37/hg19 Xq23(chrX:108922296-111549785)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 Xq23(chrX:108922296-111549785)x1

Variation ID: 1809431 Accession: VCV001809431.1

Type and length

copy number loss, -

Location

Cytogenetic: Xq23 X: 108922296-111549785 (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 31, 2022	Dec 31, 2022	Nov 21, 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.
CHRDL1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	55	224
DCX		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	288	456
PAK3		Some evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	182	357
ACSL4		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	149	314
ALG13		-	-	GRCh38 GRCh37	1091	1256
AMMECR1		-	-	GRCh38 GRCh37	49	226
CAPN6		-	-	GRCh38 GRCh37	28	199
RTL4	-	-	-	GRCh38 GRCh37	20	185
RTL9		-	-	GRCh38 GRCh37	93	263
TMEM164	-	-	-	GRCh38 GRCh37	11	181

There are 2 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	Nov 21, 2021	RCV002475804.1

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 (Nov 21, 2021)	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: SCV002773392.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Comment: This Xq23 deletion involves several protein coding genes including the 5-prime portion of ACSL4 (OMIM 300387), PAK3 (OMIM 300142), CHRDL1(OMIM 309300) and DCX (OMIM 300067). … (more) This Xq23 deletion involves several protein coding genes including the 5-prime portion of ACSL4 (OMIM 300387), PAK3 (OMIM 300142), CHRDL1(OMIM 309300) and DCX (OMIM 300067). Loss-of-function variants in CHRDL1 are associated with X-linked megalocornea in males (OMIM 309300), which is characterized by an increased corneal diameter and deep anterior chamber evident at birth with later onset of mosaic corneal degeneration (shagreen), arcus juvenilis, and presenile cataracts. Loss-of-function variants of DCX are associated with X-linked lissencephaly (OMIM 300067) in males. In addition, loss-of-function variants of ACSL4 and PAK3, have been identified in males with different forms of X-linked intellectual developmental disorders, respectively (OMIM 300387 and 300558, also refer to Cartwright 2017). A 671 kb microdeletion of Xq23 fully contained in the current deletion interval, has been reported in a boy with microsomia, midface hypoplasia, kidney dysplasia, growth retardation and some alterations of bones and heart (Lu 2021). Please note that the clinical presentation of female carriers of an X-linked pathogenic copy number variant (CNV) depends on X-inactivation patterns. References:- Cartwright et al., Clin Dysmorphol. 2017 Jan;26(1):38-40. PMID:27753653- Lu et al., J Clin Res Pediatr Endocrinol. 2021 Feb 4. PMID: 33535730 (less)

Comment:

This Xq23 deletion involves several protein coding genes including the 5-prime portion of ACSL4 (OMIM 300387), PAK3 (OMIM 300142), CHRDL1(OMIM 309300) and DCX (OMIM 300067). Loss-of-function variants in CHRDL1 are associated with X-linked megalocornea in males (OMIM 309300), which is characterized by an increased corneal diameter and deep anterior chamber evident at birth with later onset of mosaic corneal degeneration (shagreen), arcus juvenilis, and presenile cataracts. Loss-of-function variants of DCX are associated with X-linked lissencephaly (OMIM 300067) in males. In addition, loss-of-function variants of ACSL4 and PAK3, have been identified in males with different forms of X-linked intellectual developmental disorders, respectively (OMIM 300387 and 300558, also refer to Cartwright 2017). A 671 kb microdeletion of Xq23 fully contained in the current deletion interval, has been reported in a boy with microsomia, midface hypoplasia, kidney dysplasia, growth retardation and some alterations of bones and heart (Lu 2021). Please note that the clinical presentation of female carriers of an X-linked pathogenic copy number variant (CNV) depends on X-inactivation patterns. References:- Cartwright et al., Clin Dysmorphol. 2017 Jan;26(1):38-40. PMID:27753653- Lu et al., J Clin Res Pediatr Endocrinol. 2021 Feb 4. PMID: 33535730

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 Dec 31, 2022

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 Xq23(chrX:108922296-111549785)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...