NM_000517.4(HBA2):c.427T>A (p.Ter143Lys) AND alpha Thalassemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 30, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002250461.2

Allele description [Variation Report for NM_000517.4(HBA2):c.427T>A (p.Ter143Lys)]

NM_000517.4(HBA2):c.427T>A (p.Ter143Lys)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_000517.4(HBA2):c.427T>A (p.Ter143Lys)

Other names:

*142K; *143K

HGVS:

NC_000016.10:g.173598T>A
NG_000006.1:g.34461T>A
NG_046165.1:g.3337T>A
NG_059186.1:g.1948T>A
NG_059271.1:g.5752T>A
NM_000517.6:c.427T>AMANE SELECT
NP_000508.1:p.Ter143Lys
LRG_1240t1:c.427T>A
LRG_1225:g.1948T>A
LRG_1240:g.5752T>A
LRG_1240p1:p.Ter143Lys
NC_000016.9:g.223597T>A
NM_000517.4:c.427T>A

Protein change:

TER142LYS

Links:

HBVAR: 704; OMIM: 141850.0002; dbSNP: rs41464951

NCBI 1000 Genomes Browser:

rs41464951

Molecular consequence:

NM_000517.6:c.427T>A - stop lost - [Sequence Ontology: SO:0001578]

Condition(s)

Name:: alpha Thalassemia
Synonyms:: A-Thalassemia; Alpha thalassemia spectrum
Identifiers:: MONDO: MONDO:0011399; MedGen: C0002312; Orphanet: 846; OMIM: 604131

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002521042	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 30, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002521042

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 30, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From 3billion, SCV002521042.2

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

Description

The variant is observed at an extremely low frequency in the gnomAD v4.0.0 dataset (total allele frequency: <0.001%). Stop lost variant. The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least 2 similarly affected unrelated individuals (PMID: 21637442, 2372512, 8602995). The variant has been reported to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated family (PMID: 2372512). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000015626 / PMID: 21637442, 2372512, 8602995). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

#	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

Last Updated: Sep 29, 2024

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