VCV002423563.4 - ClinVar

NC_000023.10:g.(?_152014869)_(154563736_?)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.

(3)

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.

Uncertain significance

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)_(154563736_?)del

Variation ID: 2423563 Accession: VCV002423563.4

Type and length

Deletion, 2,548,868 bp

Location

Cytogenetic: Xq28 X: 152014869-154563736 (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	Jun 27, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NC_000023.10:g.(?_152014869)_(154563736_?)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 60 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.
Dyskeratosis congenita	Uncertain significance (1)	criteria provided, single submitter	Jun 27, 2022	RCV003105406.3
not provided	no classifications from unflagged records (1)	no classifications from unflagged records	-	RCV003105407.6
Anemia, nonspherocytic hemolytic, due to G6PD deficiency	no classifications from unflagged records (1)	no classifications from unflagged records	-	RCV003122393.6

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.
Uncertain significance (Jun 27, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Dyskeratosis congenita Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003793545.1 First in ClinVar: Feb 13, 2023 Last updated: Feb 13, 2023	Comment: A gross deletion of the genomic region encompassing the full coding sequence of the DKC1 gene has been identified. The current clinical and genetic evidence … (more) A gross deletion of the genomic region encompassing the full coding sequence of the DKC1 gene has been identified. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in DKC1 cause disease. 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 DKC1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Pathogenic (Jun 27, 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: SCV003790979 appears to (...more) Source: NCBI	Anemia, nonspherocytic hemolytic, due to G6PD deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003790979.2 First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023	Publications: PubMed (1) PubMed: 18177777 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the G6PD gene has been identified. Loss-of-function variants in G6PD are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the G6PD gene has been identified. Loss-of-function variants in G6PD are known to be pathogenic (PMID: 18177777). 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 G6PD-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
Uncertain significance (Jun 27, 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: SCV003792442 appears to (...more) Source: NCBI	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003792442.2 First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023	Comment: A gross deletion of the genomic region encompassing the full coding sequence of the ATP6AP1 gene has been identified. The current clinical and genetic evidence … (more) A gross deletion of the genomic region encompassing the full coding sequence of the ATP6AP1 gene has been identified. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ATP6AP1 cause disease. 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 ATP6AP1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (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 DKC1 gene has been identified. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in DKC1 cause disease. 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 DKC1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the G6PD gene has been identified. Loss-of-function variants in G6PD are known to be pathogenic (PMID: 18177777). 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 G6PD-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 ATP6AP1 gene has been identified. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ATP6AP1 cause disease. 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 ATP6AP1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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
Glucose-6-phosphate dehydrogenase deficiency.	Cappellini MD	Lancet (London, England)	2008	PMID: 18177777

Text-mined citations for this variant ...

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NC_000023.10:g.(?_152014869)_(154563736_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...