VCV003245808.1 - ClinVar

NC_000007.13:g.(?_2559496)_(2998140_?)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.

(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_000007.13:g.(?_2559496)_(2998140_?)del

Variation ID: 3245808 Accession: VCV003245808.1

Type and length

Deletion, 438,645 bp

Location

Cytogenetic: 7p22.3-22.2 7: 2559496-2998140 (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	Jun 30, 2024	Jun 29, 2024	Jun 27, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NC_000007.13:g.(?_2559496)_(2998140_?)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.
AMZ1		-	-	GRCh38 GRCh37	74	129
BRAT1		-	-	GRCh38 GRCh37	1217	1275
CARD11		-	-	GRCh38 GRCh37	940	1081
GNA12		-	-	GRCh38 GRCh37	16	72
IQCE		-	-	GRCh38 GRCh37	133	203
LFNG		-	-	GRCh38 GRCh37	239	312
TTYH3		-	-	GRCh38 GRCh37	38	86

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.
BENTA disease Severe combined immunodeficiency due to CARD11 deficiency	Pathogenic (1)	criteria provided, single submitter	Jun 27, 2023	RCV004583569.2

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 (Jun 27, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Severe combined immunodeficiency due to CARD11 deficiency BENTA disease Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: unknown	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV005065953.1 First in ClinVar: Jun 29, 2024 Last updated: Jun 29, 2024	Publications: PubMed (4) PubMed: 32581362‚ 23374270‚ 23561803‚ 26289640 Comment: For these reasons, this variant has been classified as Pathogenic. Isolated whole-gene deletions of CARD11 have not been reported in the literature. However, larger copy … (more) For these reasons, this variant has been classified as Pathogenic. Isolated whole-gene deletions of CARD11 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 32581362). A gross deletion of the genomic region encompassing the full coding sequence of the CARD11 gene has been identified. Loss-of-function variants in CARD11 are known to be pathogenic (PMID: 23374270, 23561803, 26289640). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. (less)

Comment:

For these reasons, this variant has been classified as Pathogenic. Isolated whole-gene deletions of CARD11 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 32581362). A gross deletion of the genomic region encompassing the full coding sequence of the CARD11 gene has been identified. Loss-of-function variants in CARD11 are known to be pathogenic (PMID: 23374270, 23561803, 26289640). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes.

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-genome sequencing of patients with rare diseases in a national health system.	Turro E	Nature	2020	PMID: 32581362
Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency.	Fuchs S	Blood	2015	PMID: 26289640
Whole-exome sequencing links caspase recruitment domain 11 (CARD11) inactivation to severe combined immunodeficiency.	Greil J	The Journal of allergy and clinical immunology	2013	PMID: 23561803
Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects.	Stepensky P	The Journal of allergy and clinical immunology	2013	PMID: 23374270

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NC_000007.13:g.(?_2559496)_(2998140_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...