VCV000017824.1 - ClinVar

NC_000015.10:g.(51338597_?)_(?_57376504)inv

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

NC_000015.10:g.(51338597_?)_(?_57376504)inv

Variation ID: 17824 Accession: VCV000017824.1

Type and length

Inversion, 6,037,908 bp

Location

Cytogenetic: 15q21.2-21.3 15: 51338597-57376504 (GRCh38) [ 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	Apr 4, 2013	Apr 4, 2013	May 8, 2003

HGVS

Nucleotide	Protein	Molecular consequence
NC_000015.10:g.(51338597_?)_(?_57376504)inv

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

OMIM: 107910.0010 VarSome

Comment on variant

NCBI staff provided an indeterminate HGVS expression for allelic variant 107910.0010 based on the annotation of CGNL1 and CYP19A1 on chromosome 15 (GRCH38, annotation release RS_2023_10). The inversion was reported as approximately 6.1 Mb in the paper by Shozu et al., 2003 (PubMed 12736278).

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.
TCF12		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	394	416
DMXL2		No evidence available	No evidence available	GRCh38 GRCh37	1482	1562
ARPP19		-	-	GRCh38 GRCh37	1	23
ATOSA		-	-	GRCh38 GRCh37	62	82
BCL2L10		-	-	GRCh38 GRCh37	10	43
CCPG1		-	-	GRCh38 GRCh37	-	101
CERNA1	-	-	-	GRCh38	-	31
CYP19A1		-	-	GRCh38 GRCh37	15	527
DNAAF4		-	-	GRCh38 GRCh37	22	316
DNAAF4-CCPG1	-	-	-	GRCh38	-	336

There are 171 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh38).

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.
Aromatase excess syndrome	Pathogenic (1)	no assertion criteria provided	May 8, 2003	RCV000019402.27

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 (May 08, 2003)	no assertion criteria provided Method: literature only	AROMATASE EXCESS SYNDROME Affected status: not provided Allele origin: germline	OMIM Accession: SCV000039692.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (1) PubMed: 12736278 Comment on evidence: In a 36-year-old man and his 7-year-old son with severe gynecomastia of prepubertal onset and mild hypogonadotropic hypogonadism caused by elevated estrogen levels (139300), Shozu … (more) In a 36-year-old man and his 7-year-old son with severe gynecomastia of prepubertal onset and mild hypogonadotropic hypogonadism caused by elevated estrogen levels (139300), Shozu et al. (2003) identified an inversion on 15q21.2-q21.3 that moved the promoter of the FLJ14957 gene (CGNL1; 607856) into a 5-prime position in relation to the aromatase coding region. The father in this case had progressive gynecomastia and a linear growth spurt at the age of 5 years, which was quickly followed by the development of pubic hair and penile enlargement. He stopped growing at the age of 14 years when his height was below the first percentile. He underwent bilateral mastectomy at the age of 16 years. The son was born when the father was 30 years old. Physical examination demonstrated a high-pitched voice, lack of facial hair, mastectomy scars, and unremarkable external genitalia. In the son the gynecomastia and accelerated linear growth likewise first occurred at the age of 5 years: his height and weight were above the 99th percentile, breast development was Tanner stage III, and he had normal prepubertal external genitalia. At the chronologic age of 5.5 years, his bone age was 13 years. (less)

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene.	Shozu M	The New England journal of medicine	2003	PMID: 12736278

Text-mined citations for this variant ...

Record last updated May 01, 2024

ClinVar Genomic variation as it relates to human health

NC_000015.10:g.(51338597_?)_(?_57376504)inv

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...