VCV002422157.4 - ClinVar

NC_000023.10:g.(?_152014869)_(155171615_?)del

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.

(6)

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_000023.10:g.(?_152014869)_(155171615_?)del

Variation ID: 2422157 Accession: VCV002422157.4

Type and length

Deletion, 3,156,747 bp

Location

Cytogenetic: Xq28 X: 152014869-155171615 (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, 2023	Nov 11, 2023	Oct 17, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NC_000023.10:g.(?_152014869)_(155171615_?)del

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
AVPR2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	314	576
BCAP31		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	171	422
F8		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	958	1234
FLNA		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	3145	3585
IKBKG		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	125	424
L1CAM		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1262	1527
MECP2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1896	2224
NSDHL		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh38 GRCh37	199	407
RAB39B		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	83	328

There are 65 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.
Spastic paraplegia	Pathogenic (1)	criteria provided, single submitter	Oct 17, 2022	RCV003109219.5
Frontometaphyseal dysplasia Heterotopia, periventricular, X-linked dominant Melnick-Needles syndrome Oto-palato-digital syndrome, type II	Pathogenic (1)	criteria provided, single submitter	Oct 17, 2022	RCV003109218.5
Creatine transporter deficiency	Pathogenic (1)	criteria provided, single submitter	Oct 17, 2022	RCV003119103.4
X-linked Emery-Dreifuss muscular dystrophy	Pathogenic (1)	criteria provided, single submitter	Oct 4, 2022	RCV003119102.6
3-Methylglutaconic aciduria type 2	Pathogenic (1)	criteria provided, single submitter	Oct 4, 2022	RCV003119101.5
Adrenoleukodystrophy	Pathogenic (1)	criteria provided, single submitter	Oct 17, 2022	RCV003119100.4

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.
Pathogenic (Oct 17, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Adrenoleukodystrophy Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003790062.1 First in ClinVar: Feb 13, 2023 Last updated: Feb 13, 2023	Publications: PubMed (1) PubMed: 11748843 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the ABCD1 gene has been identified. Loss-of-function variants in ABCD1 are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the ABCD1 gene has been identified. Loss-of-function variants in ABCD1 are known to be pathogenic (PMID: 11748843). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with ABCD1-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Oct 04, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	3-Methylglutaconic aciduria type 2 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003790638.2 First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023	Publications: PubMed (4) PubMed: 16427346‚ 22382802‚ 23409742‚ 19396829 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the TAZ gene has been identified. Loss-of-function variants in TAZ are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the TAZ gene has been identified. Loss-of-function variants in TAZ are known to be pathogenic (PMID: 16427346, 22382802, 23409742). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. A similar copy number variant has been observed in individual(s) with Barth syndrome (PMID: 19396829). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Oct 04, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	X-linked Emery-Dreifuss muscular dystrophy Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003790643.2 First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023	Publications: PubMed (3) PubMed: 24365856‚ 9384614‚ 10480214 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the EMD gene has been identified. Loss-of-function variants in EMD are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the EMD gene has been identified. Loss-of-function variants in EMD are known to be pathogenic (PMID: 24365856). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. A similar copy number variant has been observed in individuals with Emery‚ÄìDreifuss muscular dystrophy (EDMD) (PMID: 9384614, 10480214). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Oct 17, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Spastic paraplegia Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003793205.2 First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023	Publications: PubMed (2) PubMed: 19846429‚ 11968085 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the L1CAM gene has been identified. Loss-of-function variants in L1CAM are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the L1CAM gene has been identified. Loss-of-function variants in L1CAM are known to be pathogenic (PMID: 19846429). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. A similar copy number variant has been observed in individual(s) with X-linked hydrocephalus (PMID: 11968085). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Oct 17, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Oto-palato-digital syndrome, type II Heterotopia, periventricular, X-linked dominant Frontometaphyseal dysplasia Melnick-Needles syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003793582.2 First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023	Publications: PubMed (4) PubMed: 16684786‚ 20730588‚ 26471271‚ 29334594 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the FLNA gene has been identified. Loss-of-function variants in FLNA are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the FLNA gene has been identified. Loss-of-function variants in FLNA are known to be pathogenic (PMID: 16684786, 20730588, 26471271). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. A similar copy number variant has been observed in individual(s) with periventricular nodular heterotopia (PMID: 29334594). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Oct 17, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Creatine transporter deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003794848.1 First in ClinVar: Feb 13, 2023 Last updated: Feb 13, 2023	Publications: PubMed (4) PubMed: 22281021‚ 16601897‚ 23660394‚ 24962355 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the SLC6A8 gene has been identified. Loss-of-function variants in SLC6A8 are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the SLC6A8 gene has been identified. Loss-of-function variants in SLC6A8 are known to be pathogenic (PMID: 22281021). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. A similar copy number variant has been observed in individual(s) with clinical features of creatinine transporter deficiency (PMID: 16601897, 23660394, 24962355). For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the ABCD1 gene has been identified. Loss-of-function variants in ABCD1 are known to be pathogenic (PMID: 11748843). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with ABCD1-related conditions. For these reasons, this variant has been classified as Pathogenic.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the TAZ gene has been identified. Loss-of-function variants in TAZ are known to be pathogenic (PMID: 16427346, 22382802, 23409742). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. A similar copy number variant has been observed in individual(s) with Barth syndrome (PMID: 19396829). For these reasons, this variant has been classified as Pathogenic.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the EMD gene has been identified. Loss-of-function variants in EMD are known to be pathogenic (PMID: 24365856). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. A similar copy number variant has been observed in individuals with Emery‚ÄìDreifuss muscular dystrophy (EDMD) (PMID: 9384614, 10480214). For these reasons, this variant has been classified as Pathogenic.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the L1CAM gene has been identified. Loss-of-function variants in L1CAM are known to be pathogenic (PMID: 19846429). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. A similar copy number variant has been observed in individual(s) with X-linked hydrocephalus (PMID: 11968085). For these reasons, this variant has been classified as Pathogenic.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the FLNA gene has been identified. Loss-of-function variants in FLNA are known to be pathogenic (PMID: 16684786, 20730588, 26471271). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. A similar copy number variant has been observed in individual(s) with periventricular nodular heterotopia (PMID: 29334594). For these reasons, this variant has been classified as Pathogenic.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the SLC6A8 gene has been identified. Loss-of-function variants in SLC6A8 are known to be pathogenic (PMID: 22281021). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. A similar copy number variant has been observed in individual(s) with clinical features of creatinine transporter deficiency (PMID: 16601897, 23660394, 24962355). For these reasons, this variant has been classified as Pathogenic.

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
Thoracic aortic aneurysm in patients with loss of function Filamin A mutations: Clinical characterization, genetics, and recommendations.	Chen MH	American journal of medical genetics. Part A	2018	PMID: 29334594
47 patients with FLNA associated periventricular nodular heterotopia.	Lange M	Orphanet journal of rare diseases	2015	PMID: 26471271
RNA sequencing of creatine transporter (SLC6A8) deficient fibroblasts reveals impairment of the extracellular matrix.	Nota B	Human mutation	2014	PMID: 24962355
Emerin in health and disease.	Koch AJ	Seminars in cell & developmental biology	2014	PMID: 24365856
Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes.	Comeaux MS	Molecular genetics and metabolism	2013	PMID: 23660394
New clinical and molecular insights on Barth syndrome.	Ferri L	Orphanet journal of rare diseases	2013	PMID: 23409742
Exon-level array CGH in a large clinical cohort demonstrates increased sensitivity of diagnostic testing for Mendelian disorders.	Aradhya S	Genetics in medicine : official journal of the American College of Medical Genetics	2012	PMID: 22382802
Detection of variants in SLC6A8 and functional analysis of unclassified missense variants.	Betsalel OT	Molecular genetics and metabolism	2012	PMID: 22281021
Combined cardiological and neurological abnormalities due to filamin A gene mutation.	de Wit MC	Clinical research in cardiology : official journal of the German Cardiac Society	2011	PMID: 20730588
Genotype-phenotype correlations in L1 syndrome: a guide for genetic counselling and mutation analysis.	Vos YJ	Journal of medical genetics	2010	PMID: 19846429
A novel Alu-mediated Xq28 microdeletion ablates TAZ and partially deletes DNL1L in a patient with Barth syndrome.	Singh HR	American journal of medical genetics. Part A	2009	PMID: 19396829
Periventricular heterotopia: phenotypic heterogeneity and correlation with Filamin A mutations.	Parrini E	Brain : a journal of neurology	2006	PMID: 16684786
X-linked creatine transporter defect: a report on two unrelated boys with a severe clinical phenotype.	Anselm IA	Journal of inherited metabolic disease	2006	PMID: 16601897
Genetic analysis in patients with left ventricular noncompaction and evidence for genetic heterogeneity.	Xing Y	Molecular genetics and metabolism	2006	PMID: 16427346
Characterization of breakpoint sequences of five rearrangements in L1CAM and ABCD1 (ALD) genes.	Kutsche K	Human mutation	2002	PMID: 11968085
ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations.	Kemp S	Human mutation	2001	PMID: 11748843
Early onset of X-linked Emery-Dreifuss muscular dystrophy in a boy with emerin gene deletion.	Fujimoto S	Neuropediatrics	1999	PMID: 10480214
Emerin deletions occurring on both Xq28 inversion backgrounds.	Small K	Human molecular genetics	1998	PMID: 9384614
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Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NC_000023.10:g.(?_152014869)_(155171615_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...