VCV002424719.5 - ClinVar

NC_000005.9:g.(?_76115008)_(78281071_?)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.

(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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000005.9:g.(?_76115008)_(78281071_?)del

Variation ID: 2424719 Accession: VCV002424719.5

Type and length

Deletion, 2,166,064 bp

Location

Cytogenetic: 5q13.3-14.1 5: 76115008-78281071 (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	Feb 13, 2023	Jun 9, 2024	Mar 6, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NC_000005.9:g.(?_76115008)_(78281071_?)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.
AGGF1		-	-	GRCh38 GRCh37	50	60
AP3B1		-	-	GRCh38 GRCh37	800	810
ARSB		-	-	GRCh38 GRCh37	720	967
CRHBP		-	-	GRCh38 GRCh37	16	25
F2RL1		-	-	GRCh38 GRCh37	19	31
LHFPL2		-	-	GRCh38 GRCh37	8	20
OTP		-	-	GRCh38 GRCh37	23	35
PDE8B		-	-	GRCh38 GRCh37	280	292
S100Z		-	-	GRCh38 GRCh37	4	12
SCAMP1		-	-	GRCh38 GRCh37	3	13

There are 3 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.
Hermansky-Pudlak syndrome 2	Pathogenic (1)	criteria provided, single submitter	Mar 6, 2022	RCV003113301.5

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 (Mar 06, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hermansky-Pudlak syndrome 2 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003791388.3 First in ClinVar: Feb 13, 2023 Last updated: Jun 09, 2024	Publications: PubMed (2) PubMed: 16507770‚ 23403622 Comment: For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with AP3B1-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 AP3B1-related conditions. A gross deletion of the genomic region encompassing the full coding sequence of the AP3B1 gene has been identified. Loss-of-function variants in AP3B1 are known to be pathogenic (PMID: 16507770, 23403622). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. (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 AP3B1-related conditions. A gross deletion of the genomic region encompassing the full coding sequence of the AP3B1 gene has been identified. Loss-of-function variants in AP3B1 are known to be pathogenic (PMID: 16507770, 23403622). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes.

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 risk of hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type 2.	Jessen B	Blood	2013	PMID: 23403622
Innate immunity defects in Hermansky-Pudlak type 2 syndrome.	Fontana S	Blood	2006	PMID: 16507770

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NC_000005.9:g.(?_76115008)_(78281071_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...