NM_000517.6(HBA2):c.64G>C (p.Ala22Pro) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Apr 13, 2023
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:: RCV000985728.20

Allele description [Variation Report for NM_000517.6(HBA2):c.64G>C (p.Ala22Pro)]

NM_000517.6(HBA2):c.64G>C (p.Ala22Pro)

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.64G>C (p.Ala22Pro)

HGVS:

NC_000016.10:g.172976G>C
NG_000006.1:g.33839G>C
NG_046165.1:g.2715G>C
NG_059186.1:g.1326G>C
NG_059271.1:g.5130G>C
NM_000517.6:c.64G>CMANE SELECT
NP_000508.1:p.Ala22Pro
LRG_1240t1:c.64G>C
LRG_1225:g.1326G>C
LRG_1240:g.5130G>C
LRG_1240p1:p.Ala22Pro
NC_000016.9:g.222975G>C
NM_000517.4:c.64G>C

Protein change:

A22P

Links:

dbSNP: rs281864817

NCBI 1000 Genomes Browser:

rs281864817

Molecular consequence:

NM_000517.6:c.64G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001134201	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Apr 13, 2023)	unknown	clinical testing	PubMed (12) [See all records that cite these PMIDs] 31553106, 29627922, 24826794, 24339552, 19657841, 28784617, 2599878, 26036869, 30728682, 27020723, 22461654, 26467025
SCV001157424	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021)	Likely benign (Mar 23, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001134201

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Apr 13, 2023)

unknown

clinical testing

PubMed (12)
[See all records that cite these PMIDs]

SCV001157424

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)

Likely benign
(Mar 23, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Curating the gnomAD database: Report of novel variants in the globin-coding genes and bioinformatics analysis.

Scheps KG, Hasenahuer MA, Parisi G, Targovnik HM, Fornasari MS.

Hum Mutat. 2020 Jan;41(1):81-102. doi: 10.1002/humu.23925. Epub 2019 Oct 14.

PubMed [citation]

PMID:: 31553106

Genetics of Iranian Alpha-Thalassemia Patients: A Comprehensive Original Study.

Keikhaei B, Slehi-Fard P, Shariati G, Khosravi A.

Biochem Genet. 2018 Oct;56(5):506-521. doi: 10.1007/s10528-018-9857-6. Epub 2018 Apr 7.

PubMed [citation]

PMID:: 29627922

See all PubMed Citations (12)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001134201.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

The Hb Fontainebleau variant is reported as having normal stability (PMID: 2599878 (2009)). The variant has also been reported in a screening study of alpha thalassemia carriers (PMID: 29627922 (2018)) and has been reported individuals with microcytosis (PMID: 22461654 (2012)) and without microcytosis (PMID: 19657841 (2009)). 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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001157424.5

#	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

Last Updated: Sep 16, 2024

ClinVar

Relating variation to medicine