VCV000648517.2 - ClinVar

NC_000016.10:g.(?_172913)_(177411_?)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_000016.10:g.(?_172913)_(177411_?)del

Variation ID: 648517 Accession: VCV000648517.2

Type and length

Deletion, 4,499 bp

Location

Cytogenetic: 16p13.3 16: 172913-177411 (GRCh38) [ NCBI UCSC ] 16: 222912-227410 (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	Apr 9, 2020	Apr 9, 2020	Jan 2, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NC_000016.10:g.(?_172913)_(177411_?)del
NC_000016.9:g.(?_222912)_(227410_?)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.
HBA1		-	-	GRCh38 GRCh37	5	392
HBA2		-	-	GRCh38 GRCh37	4	346
LOC106804612	-	-	-	GRCh38	-	283
LOC106804613	-	-	-	GRCh38	1	329

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	Pathogenic (1)	criteria provided, single submitter	Jan 2, 2020	RCV000803268.3

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 (Jan 02, 2020)	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: SCV000943131.2 First in ClinVar: Aug 14, 2019 Last updated: Apr 09, 2020	Publications: PubMed (9) PubMed: 19618088‚ 16370493‚ 21381239‚ 27492767‚ 12393486‚ 1951330‚ 24826793‚ 1520607‚ 7734346 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the HBA1 gene has been identified. Although HBA1 is associated with autosomal … (more) A gross deletion of the genomic region encompassing the full coding sequence of the HBA1 gene has been identified. Although HBA1 is associated with autosomal recessive disease, a closely related gene called HBA2, when present, can compensate for the loss of HBA1. Disruption of 1 or 2 of the 4 copies of the HBA1 and HBA2 genes is typically associated with no symptoms or very mild symptoms, while disruption of at least 3 of the 4 copies is associated with overt disease (PMID: 19618088, 21381239). Consistent with this, single gene deletions of HBA1 have been observed on the opposite chromosome (in trans) from deletions encompassing both HBA1 and HBA2 in individuals with HbH disease (PMID: 16370493, 1951330, 24826793). Deletions encompassing both HBA1 and HBA2, sometimes along with other nearby genes, have been reported in many individuals affected with alpha-thalassemia and related diseases (PMID: 1520607, 7734346, 12393486, 27492767). Loss-of-function variants in HBA1 are known to be pathogenic (PMID: 12393486, 27199182). For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the HBA1 gene has been identified. Although HBA1 is associated with autosomal recessive disease, a closely related gene called HBA2, when present, can compensate for the loss of HBA1. Disruption of 1 or 2 of the 4 copies of the HBA1 and HBA2 genes is typically associated with no symptoms or very mild symptoms, while disruption of at least 3 of the 4 copies is associated with overt disease (PMID: 19618088, 21381239). Consistent with this, single gene deletions of HBA1 have been observed on the opposite chromosome (in trans) from deletions encompassing both HBA1 and HBA2 in individuals with HbH disease (PMID: 16370493, 1951330, 24826793). Deletions encompassing both HBA1 and HBA2, sometimes along with other nearby genes, have been reported in many individuals affected with alpha-thalassemia and related diseases (PMID: 1520607, 7734346, 12393486, 27492767). Loss-of-function variants in HBA1 are known to be pathogenic (PMID: 12393486, 27199182). 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
Occurrence of the - -(SEA), - -(THAI) and - -(FIL) α-Thalassemia-1 Carriers from a 7-Year Study at Ramathibodi Hospital, Bangkok, Thailand.	Pongjantharasatien K	Hemoglobin	2016	PMID: 27492767
Novel point mutation of the α2-globin gene (HBA2) and a rare 2.4 kb deletion of the α1-globin gene (HBA1), identified in two chinese patients with Hb H disease.	So CC	Hemoglobin	2014	PMID: 24826793
Gene test review. Alpha-thalassemia.	Galanello R	Genetics in medicine : official journal of the American College of Medical Genetics	2011	PMID: 21381239
Variable clinical phenotypes of alpha-thalassemia syndromes.	Singer ST	TheScientificWorldJournal	2009	PMID: 19618088
Characterization of a rare single alpha-globin gene deletion in a Chinese woman with Hb H disease.	Eng B	Hemoglobin	2005	PMID: 16370493
Hemoglobin H disease: not necessarily a benign disorder.	Chui DH	Blood	2003	PMID: 12393486
alpha-Thalassaemia in the population of Cyprus.	Baysal E	British journal of haematology	1995	PMID: 7734346
A PCR-based strategy to detect the common severe determinants of alpha thalassaemia.	Bowden DK	British journal of haematology	1992	PMID: 1520607
A novel alpha-thalassemia-2 (-2.7-kb) observed in a Chinese patient with Hb H disease.	Zhao JB	American journal of hematology	1991	PMID: 1951330

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NC_000016.10:g.(?_172913)_(177411_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...