NM_000518.5(HBB):c.112del (p.Trp38fs) AND Hemoglobinopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 9, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000781455.9

Allele description [Variation Report for NM_000518.5(HBB):c.112del (p.Trp38fs)]

NM_000518.5(HBB):c.112del (p.Trp38fs)

Genes:

LOC106099062:HBB recombination region [Gene]
HBB:hemoglobin subunit beta [Gene - OMIM - HGNC]
LOC107133510:origin of replication at HBB [Gene]

Variant type:

Deletion

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_000518.5(HBB):c.112del (p.Trp38fs)

Other names:

CD 36/37 (-T)

HGVS:

NC_000011.10:g.5226781del
NC_000011.9:g.5248010del
NG_000007.3:g.70836del
NG_042296.1:g.312del
NG_046672.1:g.4716del
NG_059281.1:g.5292del
NM_000518.5:c.112delMANE SELECT
NP_000509.1:p.Trp38fs
LRG_1232t1:c.112del
HBB:c.112delT
LRG_1232:g.5292del
LRG_1232p1:p.Trp38fs
NC_000011.10:g.5226780delA
NC_000011.9:g.5248010del
NC_000011.9:g.5248011del
NC_000011.9:g.5248011delA
NM_000518.4:c.112delT
NM_000518.5:c.112delTMANE SELECT
p.Trp38Glyfs*24

Protein change:

W38fs

Links:

Genetic Testing Registry (GTR): GTR000500319; HBVAR: 840; OMIM: 141900.0331; OMIM: 141900.0341; dbSNP: rs63750532

NCBI 1000 Genomes Browser:

rs63750532

Molecular consequence:

NM_000518.5:c.112del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hemoglobinopathy
Synonyms:: Hemoglobin disorder; Haemoglobinopathies
Identifiers:: MONDO: MONDO:0044348; MedGen: C0019045

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000919491	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jan 9, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9140720, 9401495, 1986379 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000919491

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jan 9, 2018)

germline

clinical testing

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

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

Citations

PubMed

A significant beta-thalassemia heterogeneity in the United Arab Emirates.

el-Kalla S, Mathews AR.

Hemoglobin. 1997 May;21(3):237-47.

PubMed [citation]

PMID:: 9140720

Levels of Hb A2 in heterozygotes and homozygotes for beta-thalassemia mutations: influence of mutations in the CACCC and ATAAA motifs of the beta-globin gene promoter.

Huisman TH.

Acta Haematol. 1997;98(4):187-94.

PubMed [citation]

PMID:: 9401495

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919491.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: The HBB c.112delT (p.Trp38GlyfsX24) variant results in a premature termination codon, predicted to cause a truncated or absent HBB protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant is absent in 30964 control chromosomes (gnomAD). Multiple publications have cited the variant in individuals affected with BTHAL, observed predominantly in middle eastern countries (Rund_1991, El-Kalla_1997, Huisman_1997). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.

#	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: Nov 24, 2024

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