NM_000517.6(HBA2):c.307A>C (p.Ser103Arg) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Dec 1, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV001811709.17

Allele description [Variation Report for NM_000517.6(HBA2):c.307A>C (p.Ser103Arg)]

NM_000517.6(HBA2):c.307A>C (p.Ser103Arg)

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.307A>C (p.Ser103Arg)

HGVS:

NC_000016.10:g.173478A>C
NG_000006.1:g.34341A>C
NG_046165.1:g.3217A>C
NG_059186.1:g.1828A>C
NG_059271.1:g.5632A>C
NM_000517.4:c.307A>C
NM_000517.6:c.307A>CMANE SELECT
NP_000508.1:p.Ser103Arg
LRG_1240t1:c.307A>C
LRG_1225:g.1828A>C
LRG_1240:g.5632A>C
LRG_1240p1:p.Ser103Arg
NC_000016.9:g.223477A>C

Protein change:

S103R

Links:

dbSNP: rs41321052

NCBI 1000 Genomes Browser:

rs41321052

Molecular consequence:

NM_000517.6:c.307A>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
SCV002049388	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021)	Likely benign (Feb 9, 2022)	germline	clinical testing	Citation Link,
SCV004219828	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Dec 1, 2022)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11791879, 5452728, 6547932, 7803274, 31553106, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002049388

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)

Likely benign
(Feb 9, 2022)

germline

clinical testing

Citation Link,

SCV004219828

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Dec 1, 2022)

unknown

clinical testing

PubMed (6)
[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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hb Manitoba in a Taiwanese family: a C-->A substitution at codon 102 of the alpha2-globin gene.

Chang JG, Shih MC, Liu SC, Chan WL, Peng CT.

Hemoglobin. 2001 Nov;25(4):437-9. No abstract available.

PubMed [citation]

PMID:: 11791879

alpha 102(G9) serine replaced by arginine.

Crookston JH, Farquharson HA, Kinderlerer JL, Lehmann H HEMOGLOBIN MA.

Can J Biochem. 1970 Aug;48(8):911-4. No abstract available.

PubMed [citation]

PMID:: 5452728

See all PubMed Citations (6)

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV002049388.3

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

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004219828.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The frequency of this variant in the general population, 0.0000081 (2/248256 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In vitro studies have shown that Hb Manitoba I is mildly unstable and has reduced dissociation (PMID: 7803274 (1994), 5452728 (1970)). Individuals heterozygous for this variant have a normal clinical presentation, with Hb Manitoba I accounting for 19% of total hemoglobin (PMID: 11791879 (2001), 7803274 (1994), 6547932 (1984), 5452728 (1970)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant.

#	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: Nov 3, 2024

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