VCV002671605.1 - ClinVar

Single allele

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.

Uncertain significance

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

Single allele

Variation ID: 2671605 Accession: VCV002671605.1

Type and length

Duplication, 1,832,741 bp

Location

Cytogenetic: 8p21.3 8: 20868762-22701502 (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	Dec 17, 2023	Dec 17, 2023	Mar 9, 2023

HGVS

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.
BIN3		-	-	GRCh38 GRCh37	27	122
BMP1		-	-	GRCh38 GRCh37	723	1017
C8orf58	-	-	-	GRCh38 GRCh37	8	94
CCAR2		-	-	GRCh38 GRCh37	93	186
DMTN		-	-	GRCh38 GRCh37	18	106
DOK2		-	-	GRCh38 GRCh37	43	129
EGR3		-	-	GRCh38 GRCh37	19	107
FGF17		-	-	GRCh38 GRCh37	47	134
FHIP2B		-	-	GRCh38 GRCh37	63	151
GFRA2		-	-	GRCh38 GRCh37	39	123

There are 16 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	Uncertain significance (1)	criteria provided, single submitter	Mar 9, 2023	RCV003448690.1

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.
Uncertain significance (Mar 09, 2023)	criteria provided, single submitter (ICSL CNVClassificationCriteria Aug2020) Method: clinical testing	Not Provided Affected status: unknown Allele origin: unknown	Illumina Laboratory Services, Illumina Accession: SCV004176332.1 First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023	Comment: This CNV is a 1.8 Mb duplication of 8p21.3, on chromosome 8, (seq[GRCh37]dup(8)(p21.3), chr8:g.20868762_22701502dup), which is found in a de novo state. This CNV constitutes … (more) This CNV is a 1.8 Mb duplication of 8p21.3, on chromosome 8, (seq[GRCh37]dup(8)(p21.3), chr8:g.20868762_22701502dup), which is found in a de novo state. This CNV constitutes a gain encompassing 26 protein coding genes, including full duplication of the BMP1 gene. Variants in the BMP1 gene are known to cause an autosomal recessive form of osteogenesis imperfecta (PMID: 33085247). However, there is no literature evidence to support triplosensitivity as a mechanism of disease for this gene. Patients with similar duplications in this region have not been reported in the peer-reviewed literature. A few similar sized de novo CNVs of uncertain significance or unconfirmed parentage with non-specific phenotypes have been reported in the DECIPHER database (PMID: 19344873). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as a variant of uncertain significance. (less)

Comment:

This CNV is a 1.8 Mb duplication of 8p21.3, on chromosome 8, (seq[GRCh37]dup(8)(p21.3), chr8:g.20868762_22701502dup), which is found in a de novo state. This CNV constitutes a gain encompassing 26 protein coding genes, including full duplication of the BMP1 gene. Variants in the BMP1 gene are known to cause an autosomal recessive form of osteogenesis imperfecta (PMID: 33085247). However, there is no literature evidence to support triplosensitivity as a mechanism of disease for this gene. Patients with similar duplications in this region have not been reported in the peer-reviewed literature. A few similar sized de novo CNVs of uncertain significance or unconfirmed parentage with non-specific phenotypes have been reported in the DECIPHER database (PMID: 19344873). This CNV has not been reported in controls. Based on the available evidence, this CNV is 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

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 Dec 17, 2023

ClinVar Genomic variation as it relates to human health

Single allele

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...