VCV001340527.1 - ClinVar

GRCh37/hg19 12q15-21.2(chr12:70084476-77065764)x1

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

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

GRCh37/hg19 12q15-21.2(chr12:70084476-77065764)x1

Variation ID: 1340527 Accession: VCV001340527.1

Type and length

copy number loss, 6,981,289 bp

Location

Cytogenetic: 12q15-21.2 12: 70084476-77065764 (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, 2022	Feb 13, 2022	Jan 20, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NC_000012.11:g.(?_70084476)_(77065764_?)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.
ATXN7L3B		-	-	GRCh38 GRCh37	6	19
BBS10		-	-	GRCh38 GRCh37	925	939
BEST3		-	-	GRCh38 GRCh37	42	54
CAPS2		-	-	GRCh38 GRCh37	50	79
CNOT2		-	-	GRCh38 GRCh37	42	60
GLIPR1		-	-	GRCh38 GRCh37	16	49
GLIPR1L1		-	-	GRCh38 GRCh37	-	29
GLIPR1L2		-	-	GRCh38 GRCh37	31	48
KCNC2		-	-	GRCh38 GRCh37	81	100
KCNMB4		-	-	GRCh38 GRCh37	9	27

There are 17 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh37).

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.
not provided	Pathogenic (1)	no assertion criteria provided	Jan 20, 2021	RCV001834178.1

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 (Jan 20, 2021)	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV002096462.1 First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022	Comment: The copy number loss of 12q15q21.2 involves several coding genes, including CNOT2 (OMIM 604909) and BBS10 (OMIM 610148), and is expected to cause phenotypic and/or … (more) The copy number loss of 12q15q21.2 involves several coding genes, including CNOT2 (OMIM 604909) and BBS10 (OMIM 610148), and is expected to cause phenotypic and/or developmental abnormalities. This deletion interval overlaps the region of chromosome 12q15 deletion syndrome (OMIM 618608), which is characterized by developmental delay, hypotonia, feeding problems, learning difficulties, nasal speech, skeletal anomalies, and facial dysmorphic features. Some patients may also have congenital heart defects, vision impairment or hypothyroidism. Genotype-phenotype correlation studies have proposed CNOT2 as the critical gene responsible for at least some of the core clinical features of 12q15 microdeletion syndrome, as evidenced by the phenotypic characterization of individuals with truncating variants and focal deletions of this gene (Alesi et al., Am J Med Genet A 2019;179(8):1615-1621, PMID: 31145527; Uehara et al., Am J Med Genet A 2019;179(4):659-662, PMID: 30768759; Uehara et al., Am J Med Genet A 2019;179(12):2506-2509, PMID: 31512373). Additionally, biallelic loss-of-function variants of BBS10 are associated with autosomal recessive Bardet-Biedl syndrome-10 (OMIM 615987), which is characterized by progressive retinal dystrophy, obesity, polydactyly, cognitive impairment, and renal dysplasia. (less)

Comment:

The copy number loss of 12q15q21.2 involves several coding genes, including CNOT2 (OMIM 604909) and BBS10 (OMIM 610148), and is expected to cause phenotypic and/or developmental abnormalities. This deletion interval overlaps the region of chromosome 12q15 deletion syndrome (OMIM 618608), which is characterized by developmental delay, hypotonia, feeding problems, learning difficulties, nasal speech, skeletal anomalies, and facial dysmorphic features. Some patients may also have congenital heart defects, vision impairment or hypothyroidism. Genotype-phenotype correlation studies have proposed CNOT2 as the critical gene responsible for at least some of the core clinical features of 12q15 microdeletion syndrome, as evidenced by the phenotypic characterization of individuals with truncating variants and focal deletions of this gene (Alesi et al., Am J Med Genet A 2019;179(8):1615-1621, PMID: 31145527; Uehara et al., Am J Med Genet A 2019;179(4):659-662, PMID: 30768759; Uehara et al., Am J Med Genet A 2019;179(12):2506-2509, PMID: 31512373). Additionally, biallelic loss-of-function variants of BBS10 are associated with autosomal recessive Bardet-Biedl syndrome-10 (OMIM 615987), which is characterized by progressive retinal dystrophy, obesity, polydactyly, cognitive impairment, and renal dysplasia.

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 May 17, 2022

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 12q15-21.2(chr12:70084476-77065764)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...