NM_000518.5(HBB):c.323dup (p.Asn109fs) AND beta Thalassemia

Clinical significance:Pathogenic (Last evaluated: Jul 3, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000589491.2

Allele description [Variation Report for NM_000518.5(HBB):c.323dup (p.Asn109fs)]

NM_000518.5(HBB):c.323dup (p.Asn109fs)

Genes:
LOC110006319:beta-globin gene 3' regulatory region [Gene]
HBB:hemoglobin subunit beta [Gene - OMIM - HGNC]
LOC107133510:origin of replication at HBB [Gene]
Variant type:
Duplication
Cytogenetic location:
11p15.4
Genomic location:
Preferred name:
NM_000518.5(HBB):c.323dup (p.Asn109fs)
Other names:
CD 106/107 (+G)
HGVS:
  • NC_000011.10:g.5225721dup
  • NC_000011.9:g.5246948_5246949insC
  • NG_000007.3:g.71897dup
  • NG_046672.1:g.3656dup
  • NG_053049.1:g.2042dup
  • NG_059281.1:g.6353dup
  • NM_000518.5:c.323dupMANE SELECT
  • NP_000509.1:p.Asn109fs
  • LRG_1232t1:c.323dup
  • HBB:c.321_322insG
  • LRG_1232:g.6353dup
  • LRG_1232p1:p.Asn109fs
  • NC_000011.9:g.5246948_5246949insC
  • NC_000011.9:g.5246951dup
  • NC_000011.9:g.5246951dupC
  • NM_000518.4:c.323dup
  • NM_000518.4:c.323dup
  • NM_000518.4:c.323dupG
  • p.Asn109Glnfs*32
Protein change:
N109fs
Links:
HBVAR: 945; OMIM: 141900.0329; dbSNP: rs35225141
NCBI 1000 Genomes Browser:
rs35225141
Molecular consequence:
  • NM_000518.5:c.323dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000697119Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Jul 3, 2017)
germlineclinical testing

PubMed (13)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV001244495The ITHANET community portal, The Cyprus Institute of Neurology and Geneticsno assertion criteria providedPathogenic
(Nov 25, 2019)
germlinecuration

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

ThalassoChip, an array mutation and single nucleotide polymorphism detection tool for the diagnosis of β-thalassaemia.

Shammas C, Papasavva T, Felekis X, Christophorou C, Roomere H, Synodinos JT, Kanavakis E, El-Khateeb M, Hamamy H, Mahmoud T, Shboul M, El Beshlawy A, Filon D, Hussein IR, Galanello R, Romeo G, Kleanthous M.

Clin Chem Lab Med. 2010 Dec;48(12):1713-8. doi: 10.1515/CCLM.2010.331. Epub 2010 Aug 13.

PubMed [citation]
PMID:
20704537

Analysis of beta globin mutations in the Indian population: presence of rare and novel mutations and region-wise heterogeneity.

Edison ES, Shaji RV, Devi SG, Moses A, Viswabandhya A, Mathews V, George B, Srivastava A, Chandy M.

Clin Genet. 2008 Apr;73(4):331-7. doi: 10.1111/j.1399-0004.2008.00973.x. Epub 2008 Feb 20.

PubMed [citation]
PMID:
18294253
See all PubMed Citations (15)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697119.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (13)

Description

Variant summary: The c.323dupG (p.Asn109Glnfs) variant in HBB gene is a frameshift change that is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. The variant is absent from the large control population dataset of ExAC, but is present at a low frequency in gnomAD dataset (0.000007; 2/276928 chrs tested), which does not exceed exceed the estimated maximal expected allele frequency of a pathogenic variant (0.011). The variant has been reported in several affected individuals presented with b-thalassemia major via published reports and is cited by reputable databases/clinical laboratories as Pathogenic. Taking together, the variant was classified as Pathogenic.

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

From The ITHANET community portal, The Cyprus Institute of Neurology and Genetics, SCV001244495.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 27, 2021

Support Center