VCV001449359.8 - ClinVar

NC_000011.9:g.(?_64522783)_(66283694_?)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.(?_64522783)_(66283694_?)del

Variation ID: 1449359 Accession: VCV001449359.8

Type and length

Deletion, 1,760,912 bp

Location

Cytogenetic: 11q13.1-13.2 11: 64522783-66283694 (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	Jun 9, 2024	Jul 1, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NC_000011.9:g.(?_64522783)_(66283694_?)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.
MEN1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2580	2601
PACS1		No evidence available	No evidence available	GRCh38 GRCh37	776	814
AP5B1		-	-	GRCh38 GRCh37	71	86
ARL2		-	-	GRCh38 GRCh37	-	26
ATG2A		-	-	GRCh38 GRCh37	165	179
B4GAT1		-	-	GRCh38 GRCh37	195	218
BANF1		-	-	GRCh38 GRCh37	27	47
BATF2		-	-	GRCh38 GRCh37	19	31
BBS1		-	-	GRCh38 GRCh37	454	1124
BRMS1		-	-	GRCh38 GRCh37	31	48

There are 73 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.
Bardet-Biedl syndrome	Pathogenic (1)	criteria provided, single submitter	Jul 1, 2022	RCV002014493.8
Glycogen storage disease, type V	Pathogenic (1)	criteria provided, single submitter	Jul 1, 2022	RCV002004587.6

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 (Jul 01, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Glycogen storage disease, type V Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002231000.4 First in ClinVar: Mar 28, 2022 Last updated: Jun 09, 2024	Publications: PubMed (2) PubMed: 8316268‚ 16786513 Comment: For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PYGM-related conditions. … (more) For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PYGM-related conditions. This sequence change is a complex rearrangement involving exon(s) 1-7 of the PYGM gene. It does not change the copy number of any exons. Although the exact nature of the event is unknown, it is likely that this is a large inversion event including exon(s) 1-7, that would either disrupt the transcription or result in a truncated protein product. Loss-of-function variants in PYGM are known to be pathogenic (PMID: 8316268, 16786513). (less)
Pathogenic (Jul 01, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Bardet-Biedl syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002229918.4 First in ClinVar: Mar 28, 2022 Last updated: Jun 09, 2024	Publications: PubMed (3) PubMed: 12118255‚ 21520335‚ 27032803 Comment: This sequence change is a complex rearrangement involving exon(s) 1-7 of the BBS1 gene. It does not change the copy number of any exons. Although … (more) This sequence change is a complex rearrangement involving exon(s) 1-7 of the BBS1 gene. It does not change the copy number of any exons. Although the exact nature of the event is unknown, it is likely that this is a large inversion event including exon(s) 1-7, that would either disrupt the transcription or result in a truncated protein product. Loss-of-function variants in BBS1 are known to be pathogenic (PMID: 12118255, 21520335, 27032803). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with BBS1-related conditions. (less)

Comment:

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PYGM-related conditions. This sequence change is a complex rearrangement involving exon(s) 1-7 of the PYGM gene. It does not change the copy number of any exons. Although the exact nature of the event is unknown, it is likely that this is a large inversion event including exon(s) 1-7, that would either disrupt the transcription or result in a truncated protein product. Loss-of-function variants in PYGM are known to be pathogenic (PMID: 8316268, 16786513).

Comment:

This sequence change is a complex rearrangement involving exon(s) 1-7 of the BBS1 gene. It does not change the copy number of any exons. Although the exact nature of the event is unknown, it is likely that this is a large inversion event including exon(s) 1-7, that would either disrupt the transcription or result in a truncated protein product. Loss-of-function variants in BBS1 are known to be pathogenic (PMID: 12118255, 21520335, 27032803). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with BBS1-related conditions.

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
Improving the management of Inherited Retinal Dystrophies by targeted sequencing of a population-specific gene panel.	Bravo-Gil N	Scientific reports	2016	PMID: 27032803
U1 snRNA-mediated gene therapeutic correction of splice defects caused by an exceptionally mild BBS mutation.	Schmid F	Human mutation	2011	PMID: 21520335
McArdle disease: the mutation spectrum of PYGM in a large Italian cohort.	Bruno C	Human mutation	2006	PMID: 16786513
Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome.	Mykytyn K	Nature genetics	2002	PMID: 12118255
Molecular genetic heterogeneity of myophosphorylase deficiency (McArdle's disease).	Tsujino S	The New England journal of medicine	1993	PMID: 8316268

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.(?_64522783)_(66283694_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...