VCV001455268.3 - ClinVar

NC_000011.9:g.(?_101323686)_(103349981_?)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.

(2)

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_000011.9:g.(?_101323686)_(103349981_?)del

Variation ID: 1455268 Accession: VCV001455268.3

Type and length

Deletion, 2,026,296 bp

Location

Cytogenetic: 11q22.1-22.3 11: 101323686-103349981 (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	Mar 28, 2022	Nov 11, 2023	Oct 6, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NC_000011.9:g.(?_101323686)_(103349981_?)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.
YAP1		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	74	100
ANGPTL5		-	-	GRCh38 GRCh37	21	50
BIRC2		-	-	GRCh38 GRCh37	44	70
BIRC3		-	-	GRCh38 GRCh37	33	58
CEP126		-	-	GRCh38 GRCh37	67	98
CFAP300		-	-	GRCh38 GRCh37	90	114
DCUN1D5		-	-	GRCh38 GRCh37	2	28
DYNC2H1		-	-	GRCh38 GRCh37	3562	3595
MMP1		-	-	GRCh38 GRCh37	87	113
MMP10		-	-	GRCh38 GRCh37	42	68

There are 9 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.
Jeune thoracic dystrophy	no classifications from unflagged records (1)	no classifications from unflagged records	-	RCV001942288.6
not provided	Pathogenic (1)	criteria provided, single submitter	Oct 6, 2021	RCV001942287.4

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 (Oct 06, 2021)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002242470.3 First in ClinVar: Mar 28, 2022 Last updated: Nov 11, 2023	Publications: PubMed (2) PubMed: 24781753‚ 31413057 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the MMP13 gene has been identified. Loss-of-function variants in MMP13 are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the MMP13 gene has been identified. Loss-of-function variants in MMP13 are known to be pathogenic (PMID: 24781753, 31413057). 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 MMP13-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Oct 06, 2021)	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: SCV002228675 appears to (...more) Source: NCBI	Jeune thoracic dystrophy Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002228675.3 First in ClinVar: Mar 28, 2022 Last updated: Nov 11, 2023	Publications: PubMed (2) PubMed: 23339108‚ 32753734 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the DYNC2H1 gene has been identified. Loss-of-function variants in DYNC2H1 are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the DYNC2H1 gene has been identified. Loss-of-function variants in DYNC2H1 are known to be pathogenic (PMID: 23339108, 32753734). 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 DYNC2H1-related conditions. For these reasons, this variant has been classified as Pathogenic. (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 MMP13 gene has been identified. Loss-of-function variants in MMP13 are known to be pathogenic (PMID: 24781753, 31413057). 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 MMP13-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 DYNC2H1 gene has been identified. Loss-of-function variants in DYNC2H1 are known to be pathogenic (PMID: 23339108, 32753734). 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 DYNC2H1-related conditions. For these reasons, this variant has been classified as Pathogenic.

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
DYNC2H1 hypomorphic or retina-predominant variants cause nonsyndromic retinal degeneration.	Vig A	Genetics in medicine : official journal of the American College of Medical Genetics	2020	PMID: 32753734
Metaphyseal dysplasia, Spahr type: a mimicker of rickets.	Balasubramaniyan M	BMJ case reports	2019	PMID: 31413057
Exome sequencing reveals a nonsense mutation in MMP13 as a new cause of autosomal recessive metaphyseal anadysplasia.	Li D	European journal of human genetics : EJHG	2015	PMID: 24781753
Asphyxiating thoracic dysplasia: clinical and molecular review of 39 families.	Baujat G	Journal of medical genetics	2013	PMID: 23339108

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NC_000011.9:g.(?_101323686)_(103349981_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...