NM_000517.6(HBA2):c.60del (p.His21fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 17, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000341094.5

Allele description [Variation Report for NM_000517.6(HBA2):c.60del (p.His21fs)]

NM_000517.6(HBA2):c.60del (p.His21fs)

Genes:

LOC106804612:hemoglobin subunit alpha 2 recombination region [Gene]
HBA2:hemoglobin subunit alpha 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_000517.6(HBA2):c.60del (p.His21fs)

HGVS:

NC_000016.10:g.172972del
NG_000006.1:g.33835del
NG_046165.1:g.2711del
NG_059186.1:g.1322del
NG_059271.1:g.5126del
NM_000517.6:c.60delMANE SELECT
NP_000508.1:p.His21fs
LRG_1240t1:c.60del
LRG_1225:g.1322del
LRG_1240:g.5126del
LRG_1240p1:p.His21fs
NC_000016.10:g.172972delG
NC_000016.9:g.222971del
NM_000517.4:c.60delG
NM_000517.6:c.60delGMANE SELECT
p.His21Thrfs*29

Protein change:

H21fs

Links:

dbSNP: rs886041399

NCBI 1000 Genomes Browser:

rs886041399

Molecular consequence:

NM_000517.6:c.60del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000329991	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 17, 2023)	germline	clinical testing	Citation Link,
SCV000601221	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Apr 5, 2023)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 14508795, 22943743, 16798638, 30830998, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000329991

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 17, 2023)

germline

clinical testing

Citation Link,

SCV000601221

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Apr 5, 2023)

unknown

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular spectrum of alpha-thalassemia in the Iranian population of Hormozgan: three novel point mutation defects.

Harteveld CL, Yavarian M, Zorai A, Quakkelaar ED, van Delft P, Giordano PC.

Am J Hematol. 2003 Oct;74(2):99-103.

PubMed [citation]

PMID:: 14508795

α-thalassemia trait caused by frameshift mutations in exon 2 of the α2-globin gene: HBA2:c.131delT and HBA2:c.143delA.

Finlayson J, Ghassemifar R, Holmes P, Grey D, Newbound C, Pell N, Jennens M, Greenwood L, Beilby J.

Hemoglobin. 2012;36(5):511-5.

PubMed [citation]

PMID:: 22943743

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV000329991.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 16798638, 29627922, 22943743, 36567661, 14508795)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601221.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The HBA2 c.60del (p.His21Thrfs*29) frameshift variant (also known as CD19(-G)) causes the premature termination of HBA2 protein synthesis. In addition, it has been reported in the published literature in several newborns with visibly elevated Hb Bart’s levels and is described to lead to an alpha-thalassemia phenotype (PMID: 14508795 (2003)). The variant was also reported in a heterozygous individual having an alpha+ thalassemia trait phenotype (PMID: 30830998 (2019)). Therefore, the variant is classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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