NM_000517.6(HBA2):c.421T>C (p.Tyr141His) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 31, 2023
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:: RCV003477259.1

Allele description [Variation Report for NM_000517.6(HBA2):c.421T>C (p.Tyr141His)]

NM_000517.6(HBA2):c.421T>C (p.Tyr141His)

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_000517.6(HBA2):c.421T>C (p.Tyr141His)

HGVS:

NC_000016.10:g.173592T>C
NG_000006.1:g.34455T>C
NG_046165.1:g.3331T>C
NG_059186.1:g.1942T>C
NG_059271.1:g.5746T>C
NG_115661.1:g.348T>C
NM_000517.6:c.421T>CMANE SELECT
NP_000508.1:p.Tyr141His
LRG_1240t1:c.421T>C
LRG_1225:g.1942T>C
LRG_1240:g.5746T>C
LRG_1240p1:p.Tyr141His
NC_000016.9:g.223591T>C
NM_000517.4:c.421T>C

Protein change:

Y141H

Molecular consequence:

NM_000517.6:c.421T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV004219832	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely pathogenic (May 31, 2023)	unknown	clinical testing	PubMed (10) [See all records that cite these PMIDs] 32420790, 1428951, 1390944, 8117715, 24200101, 21974826, 9930984, 11132645, 16368110, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004219832

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Likely pathogenic
(May 31, 2023)

unknown

clinical testing

PubMed (10)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

In Silico Analysis of the Effects of Point Mutations on α-Globin: Implications for α-Thalassemia.

Horri-Naceur A, Timson DJ.

Hemoglobin. 2020 Mar;44(2):89-103. doi: 10.1080/03630269.2020.1739067. Epub 2020 May 18.

PubMed [citation]

PMID:: 32420790

Hb Ethiopia or alpha 2(140)(HC2)Tyr----His beta 2.

Webber BB, Wilson JB, Gu LH, Huisman TH.

Hemoglobin. 1992;16(5):441-3. No abstract available.

PubMed [citation]

PMID:: 1428951

See all PubMed Citations (10)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004219832.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

In the published literature, this variant was discovered in a newborn baby of Ethiopian decent. The variant was also reported in the baby's father who is described as having normal hematological parameters, though with an elevated MCV (PMID: 1428951 (1992)). This variant results in decreased Bohr effect, decreased cooperativity, and increased oxygen affinity. The frequency of this variant in the general population, 0.0000067 (1/148948 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, this variant is classified as likely 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: Sep 1, 2024

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