VCV002500712.1 - ClinVar

NC_000023.11:g.153714363_153781647del

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

NC_000023.11:g.153714363_153781647del

Variation ID: 2500712 Accession: VCV002500712.1

Type and length

Deletion, 67,285 bp

Location

Cytogenetic: Xq28 X: 153714363-153781647 (GRCh38) [ 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	May 7, 2023	May 6, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NC_000023.11:g.153714363_153781647del

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.
ABCD1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1526	1772
BCAP31		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	171	422
LOC130068830	-	-	-	GRCh38	-	111
LOC130068831	-	-	-	GRCh38	-	116
LOC130068832	-	-	-	GRCh38	-	110
LOC130068833	-	-	-	GRCh38	-	111
LOC130068834	-	-	-	GRCh38	-	111
PLXNB3		-	-	GRCh38 GRCh37	192	445
PLXNB3-AS1	-	-	-	GRCh38	-	119
SRPK3		-	-	GRCh38 GRCh37	52	297

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.
Severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome	Pathogenic (1)	criteria provided, single submitter	-	RCV003225624.1

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 (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome Affected status: yes Allele origin: de novo	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute Accession: SCV003921813.1 First in ClinVar: May 06, 2023 Last updated: May 06, 2023	Comment: - This copy number variant (CNV) results in the deletion of the entire ABCD1 gene and partial deletion of the BCAP31 gene (previously known as … (more) - This copy number variant (CNV) results in the deletion of the entire ABCD1 gene and partial deletion of the BCAP31 gene (previously known as DXS1375E). This is predicted to cause loss of function of both proteins. - Other CNVs and variants predicted to result in nonsense-mediated decay, comparable to the one identified in this case, have very strong previous evidence for pathogenicity in patients with contiguous ABCD1/DXS1375E deletion syndrome (CADDS) (PMID: 22994209, PMID: 11992258, PMID: 33603160, ClinVar). - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in multiple de novo hemizygous individuals with CADDS and has been described as pathogenic (ClinVar, PMID: 33603160, PMID: 11992258). - This variant has been shown to be de novo in the proband (parental status confirmed, by trio analysis). Additional information: - Loss of function is a known mechanism of disease in this deleted region and is associated with contiguous ABCD1/DXS1375E deletion syndrome (CADDS). - This gene is associated with X-linked recessive disease. - This variant is hemizygous. - Variant is absent from gnomAD (both v2 and v3). (less)

Comment:

- This copy number variant (CNV) results in the deletion of the entire ABCD1 gene and partial deletion of the BCAP31 gene (previously known as DXS1375E). This is predicted to cause loss of function of both proteins. - Other CNVs and variants predicted to result in nonsense-mediated decay, comparable to the one identified in this case, have very strong previous evidence for pathogenicity in patients with contiguous ABCD1/DXS1375E deletion syndrome (CADDS) (PMID: 22994209, PMID: 11992258, PMID: 33603160, ClinVar). - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in multiple de novo hemizygous individuals with CADDS and has been described as pathogenic (ClinVar, PMID: 33603160, PMID: 11992258). - This variant has been shown to be de novo in the proband (parental status confirmed, by trio analysis). Additional information: - Loss of function is a known mechanism of disease in this deleted region and is associated with contiguous ABCD1/DXS1375E deletion syndrome (CADDS). - This gene is associated with X-linked recessive disease. - This variant is hemizygous. - Variant is absent from gnomAD (both v2 and v3).

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 Oct 15, 2023

ClinVar Genomic variation as it relates to human health

NC_000023.11:g.153714363_153781647del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...