NM_000518.5(HBB):c.59A>G (p.Asn20Ser) AND beta Thalassemia

Clinical significance:Pathogenic (Last evaluated: Mar 20, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000020338.2

Allele description [Variation Report for NM_000518.5(HBB):c.59A>G (p.Asn20Ser)]

NM_000518.5(HBB):c.59A>G (p.Asn20Ser)

Genes:
LOC106099062:HBB recombination region [Gene]
HBB:hemoglobin subunit beta [Gene - OMIM - HGNC]
LOC107133510:origin of replication at HBB [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.4
Genomic location:
Preferred name:
NM_000518.5(HBB):c.59A>G (p.Asn20Ser)
Other names:
N19S; 19A>G
HGVS:
  • NC_000011.10:g.5226963T>C
  • NG_000007.3:g.70653A>G
  • NG_042296.1:g.494T>C
  • NG_046672.1:g.4898T>C
  • NG_059281.1:g.5109A>G
  • NM_000518.5:c.59A>GMANE SELECT
  • NP_000509.1:p.Asn20Ser
  • LRG_1232t1:c.59A>G
  • LRG_1232:g.5109A>G
  • LRG_1232p1:p.Asn20Ser
  • NC_000011.9:g.5248193T>C
  • NM_000518.4:c.59A>G
  • P68871:p.Asn20Ser
  • c.56A>G
  • p.Asn19Ser
Protein change:
N20S; ASN19SER
Links:
UniProtKB: P68871#VAR_002888; OMIM: 141900.0168; dbSNP: rs33972047
NCBI 1000 Genomes Browser:
rs33972047
Molecular consequence:
  • NM_000518.5:c.59A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
beta Thalassemia (BTHAL)
Synonyms:
Cooley's anemia; Erythroblastic anemia; Mediterranean anemia
Identifiers:
MedGen: C0005283; Orphanet: 848; OMIM: 613985

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000040714GeneReviewsno assertion criteria providedPathogenic
(May 14, 2015)
germlineliterature only

Citation Link,

SCV000697141Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Mar 20, 2017)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
Thaigermlineunknownnot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Abnormal processing of beta-Malay globin RNA.

Gonzalez-Redondo JM, Brickner HE, Atweh GF.

Biochem Biophys Res Commun. 1989 Aug 30;163(1):8-13.

PubMed [citation]
PMID:
2775294

Molecular characterization of beta-globin gene mutations in Malay patients with Hb E-beta-thalassaemia and thalassaemia major.

Yang KG, Kutlar F, George E, Wilson JB, Kutlar A, Stoming TA, Gonzalez-Redondo JM, Huisman TH.

Br J Haematol. 1989 May;72(1):73-80.

PubMed [citation]
PMID:
2736244
See all PubMed Citations (3)

Details of each submission

From GeneReviews, SCV000040714.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Thainot providednot providednot providedliterature onlynot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697141.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: The HBB c.59A>G (p.Asn20Ser) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). 5/5 splice prediction tools predict that this variant strengthens a cryptic 5' splicing donor site and affects normal splicing. This prediction has been confirmed by at least one functional study (Gonzalez-Redondo_1989). This variant has been found in multiple patients with beta thalassemia (Yang_1989 and Rujito_2015) and is absent in 121362 control chromosomes. In addition, multiple reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.

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

Last Updated: Nov 27, 2021

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