VCV000583459.8 - ClinVar

NC_000015.10:g.(?_22786657)_(23032029_?)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.

Uncertain significance

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000015.10:g.(?_22786657)_(23032029_?)del

Variation ID: 583459 Accession: VCV000583459.8

Type and length

Deletion, 245,373 bp

Location

Cytogenetic: 15q11.2 15: 22786657-23032029 (GRCh38) [ NCBI UCSC ] 15: 22841039-23086411 (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	Oct 10, 2018	Nov 11, 2023	Sep 16, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NC_000015.10:g.(?_22786657)_(23032029_?)del
NC_000015.9:g.(?_22841039)_(23086411_?)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.
NIPA1		No evidence available	No evidence available	GRCh38 GRCh38 GRCh37	272	682
NIPA2		No evidence available	No evidence available	GRCh38 GRCh38 GRCh37	56	390
CYFIP1		-	-	GRCh38 GRCh38 GRCh38 GRCh37	112	453
LOC112272575	-	-	-	GRCh38 GRCh38	-	129
LOC126862074	-	-	-	GRCh38 GRCh38	-	120
LOC130056709	-	-	-	GRCh38 GRCh38	-	179
LOC130056710	-	-	-	GRCh38 GRCh38	-	112
LOC130056711	-	-	-	GRCh38 GRCh38	-	110
LOC130056712	-	-	-	GRCh38 GRCh38	-	111
LOC130056713	-	-	-	GRCh38 GRCh38	-	122

There are 6 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh38 , 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.
Hereditary spastic paraplegia 6	no classifications from unflagged records (1)	no classifications from unflagged records	-	RCV000707782.4
not provided	Uncertain significance (1)	criteria provided, single submitter	Sep 16, 2021	RCV001861923.7

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 (Sep 16, 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: SCV002228612.3 First in ClinVar: Mar 28, 2022 Last updated: Nov 11, 2023	Publications: PubMed (3) PubMed: 17268193‚ 23032108‚ 25689425 Comment: This variant is a gross deletion of the genomic region encompassing exon(s) 5-23 of the TUBGCP5 gene, which includes the termination codon. This deletion extends … (more) This variant is a gross deletion of the genomic region encompassing exon(s) 5-23 of the TUBGCP5 gene, which includes the termination codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. Isolated whole-gene deletions of TUBGCP5 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 17268193, 23032108, 25689425). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Uncertain significance (Apr 05, 2018)	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: SCV000836892 appears to (...more) Source: NCBI	Spastic paraplegia 6 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000836892.1 First in ClinVar: Oct 10, 2018 Last updated: Oct 10, 2018	Publications: PubMed (4) PubMed: 28492532‚ 17268193‚ 25689425‚ 23032108 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the NIPA1 gene has been identified. The boundaries of this event are … (more) A gross deletion of the genomic region encompassing the full coding sequence of the NIPA1 gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletions of NIPA1 have not been reported in the literature. However, larger copy number events that include this gene have been reported in individuals affected with neurological dysfunction, developmental and language delay are the most commonly associated findings followed by motor delay, ADD/ADHD and autism spectrum disorder (PMID: 17268193, 25689425, 23032108). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NIPA1 cause disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more

Comment:

This variant is a gross deletion of the genomic region encompassing exon(s) 5-23 of the TUBGCP5 gene, which includes the termination codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. Isolated whole-gene deletions of TUBGCP5 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 17268193, 23032108, 25689425). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the NIPA1 gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletions of NIPA1 have not been reported in the literature. However, larger copy number events that include this gene have been reported in individuals affected with neurological dysfunction, developmental and language delay are the most commonly associated findings followed by motor delay, ADD/ADHD and autism spectrum disorder (PMID: 17268193, 25689425, 23032108). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NIPA1 cause disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been 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

Title	Author	Journal	Year	Link
The 15q11.2 BP1-BP2 microdeletion syndrome: a review.	Cox DM	International journal of molecular sciences	2015	PMID: 25689425
Application of custom-designed oligonucleotide array CGH in 145 patients with autistic spectrum disorders.	Wiśniowiecka-Kowalnik B	European journal of human genetics : EJHG	2013	PMID: 23032108
Detection of a novel familial deletion of four genes between BP1 and BP2 of the Prader-Willi/Angelman syndrome critical region by oligo-array CGH in a child with neurological disorder and speech impairment.	Murthy SK	Cytogenetic and genome research	2007	PMID: 17268193

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NC_000015.10:g.(?_22786657)_(23032029_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...