NM_000517.6(HBA2):c.242T>G (p.Leu81Arg) AND none provided

Clinical significance:Likely pathogenic (Last evaluated: Dec 16, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001284977.1

Allele description [Variation Report for NM_000517.6(HBA2):c.242T>G (p.Leu81Arg)]

NM_000517.6(HBA2):c.242T>G (p.Leu81Arg)

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.242T>G (p.Leu81Arg)
HGVS:
  • NC_000016.10:g.173271T>G
  • NG_000006.1:g.34134T>G
  • NG_046165.1:g.3010T>G
  • NG_059186.1:g.1621T>G
  • NG_059271.1:g.5425T>G
  • NM_000517.6:c.242T>GMANE SELECT
  • NP_000508.1:p.Leu81Arg
  • LRG_1240t1:c.242T>G
  • LRG_1225:g.1621T>G
  • LRG_1240:g.5425T>G
  • LRG_1240p1:p.Leu81Arg
  • NC_000016.9:g.223270T>G
Protein change:
L81R
Links:
Molecular consequence:
  • NM_000517.6:c.242T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
none provided
Identifiers:
MedGen: CN235283

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001471079ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Likely pathogenic
(Dec 16, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV001471079.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The Hb Ann Arbor variant (HBA2: c.242T>G; p.Leu81Arg, also known as Leu80Arg when numbered from the mature protein rs281864863) is reported in the literature in two brothers affected with hemolytic microcytic anemia (Adams 1972, Adams 1974, HbVar database). Both affected brothers carried Hb Ann Arbor in the heterozygous state and were presumed to carry an additional undetermined alpha-thalassemia allele in trans, although this second allele was not determined (Adams 1974). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The affected brothers with Hb Ann Arbor exhibited 10-15% abnormal hemoglobin, while other family members that carried Hb Ann Arbor exhibited 2-5% abnormal hemoglobin (Adams 1974). The proportions of abnormal hemoglobin in heterozygous carriers, heat stability assays, and functional assays of protein synthesis all suggest Hb Ann Arbor is unstable and rapidly degraded (Adams 1972, Adams 1974). Based on available information, this variant is considered to be likely pathogenic. References: Link to Hb Ann Arbor in HbVar database: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=123 Adams JG 3rd et al. Biosynthesis of hemoglobin Ann Arbor: evidence for catabolic and feedback regulation. Science. 1972 Jun 30;176(4042):1427-9. Adams JG 3rd. Hemoglobin Ann Arbor: disturbance in the coordinated biosynthesis of globin chains? Ann N Y Acad Sci. 1974 Nov 29;241(0):232-41.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 30, 2021

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