VCV002422978.4 - ClinVar

NC_000023.10:g.(?_46618120)_(48549553_?)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.

(2)

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.(?_46618120)_(48549553_?)del

Variation ID: 2422978 Accession: VCV002422978.4

Type and length

Deletion, 1,931,434 bp

Location

Cytogenetic: Xp11.23 X: 46618120-48549553 (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	Mar 3, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NC_000023.10:g.(?_46618120)_(48549553_?)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.
EBP		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	178	346
PORCN		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	155	322
RP2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	357	568
SYN1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	505	681
FTSJ1		Some evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	85	250
ZNF41		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	78	232
ELK1		No evidence available	No evidence available	GRCh38 GRCh37	24	170
SLC38A5		No evidence available	No evidence available	GRCh38 GRCh37	19	184
ZNF81		No evidence available	No evidence available	GRCh38 GRCh37	56	212
ARAF		-	-	GRCh38 GRCh37	36	187

There are 27 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.
Thrombocytopenia 1 Wiskott-Aldrich syndrome X-linked severe congenital neutropenia	no classifications from unflagged records (1)	no classifications from unflagged records	-	RCV003111118.6
not provided	Pathogenic (1)	criteria provided, single submitter	Mar 3, 2022	RCV003122288.3

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 (Mar 03, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003791165.2 First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023	Publications: PubMed (6) PubMed: 8530058‚ 9476131‚ 10698340‚ 10909851‚ 19328743‚ 22229731 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the CFP gene has been identified. Loss-of-function variants in CFP are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the CFP gene has been identified. Loss-of-function variants in CFP are known to be pathogenic (PMID: 8530058, 9476131, 10698340, 10909851, 19328743, 22229731). 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 CFP-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Mar 03, 2022)	Flagged submission flagged submission (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing Reason: This record appears to be redundant with a more recent record from the same submitter. Notes: SCV003793134 appears to (...more) Source: NCBI	Wiskott-Aldrich syndrome X-linked severe congenital neutropenia Thrombocytopenia 1 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003793134.2 First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023	Publications: PubMed (3) PubMed: 15284122‚ 12969986‚ 28901403 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the WAS gene has been identified. Loss-of-function variants in WAS are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the WAS gene has been identified. Loss-of-function variants in WAS are known to be pathogenic (PMID: 15284122). 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 Wiskott-Aldrich syndrome (PMID: 12969986, 28901403). For these reasons, this variant has been classified as Pathogenic. (less)
Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the CFP gene has been identified. Loss-of-function variants in CFP are known to be pathogenic (PMID: 8530058, 9476131, 10698340, 10909851, 19328743, 22229731). 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 CFP-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 WAS gene has been identified. Loss-of-function variants in WAS are known to be pathogenic (PMID: 15284122). 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 Wiskott-Aldrich syndrome (PMID: 12969986, 28901403). 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
Whole Wiskott‑Aldrich syndrome protein gene deletion identified by high throughput sequencing.	He X	Molecular medicine reports	2017	PMID: 28901403
A novel mutation W388X underlying properdin deficiency in a Finnish family.	Helminen M	Scandinavian journal of immunology	2012	PMID: 22229731
Properdin deficiency associated with recurrent otitis media and pneumonia, and identification of male carrier with Klinefelter syndrome.	Schejbel L	Clinical immunology (Orlando, Fla.)	2009	PMID: 19328743
Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation.	Jin Y	Blood	2004	PMID: 15284122
Clinical course of patients with WASP gene mutations.	Imai K	Blood	2004	PMID: 12969986
Molecular characterisation of 10 Dutch properdin type I deficient families: mutation analysis and X-inactivation studies.	van den Bogaard R	European journal of human genetics : EJHG	2000	PMID: 10909851
Properdin deficiency: molecular basis and disease association.	Fijen CA	Molecular immunology	1999	PMID: 10698340
Human properdin deficiency has a heterogeneous genetic background.	Truedsson L	Immunopharmacology	1997	PMID: 9476131
Sequence-based analysis of properdin deficiency: identification of point mutations in two phenotypic forms of an X-linked immunodeficiency.	Westberg J	Genomics	1995	PMID: 8530058

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.(?_46618120)_(48549553_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...