NM_000518.5(HBB):c.51del (p.Lys18fs) AND Hemoglobinopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 31, 2016
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:: RCV000590756.9

Allele description [Variation Report for NM_000518.5(HBB):c.51del (p.Lys18fs)]

NM_000518.5(HBB):c.51del (p.Lys18fs)

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.51del (p.Lys18fs)

Other names:

CD 16 GGC>GG-

HGVS:

NC_000011.10:g.5226971del
NG_000007.3:g.70645del
NG_042296.1:g.502del
NG_046672.1:g.4906del
NG_059281.1:g.5101del
NM_000518.5:c.51delMANE SELECT
NP_000509.1:p.Lys18fs
LRG_1232t1:c.51del
HBB:c.51delC
LRG_1232:g.5101del
LRG_1232p1:p.Lys18fs
NC_000011.9:g.5248201del
NC_000011.9:g.5248201delG
NM_000518.4:c.51del
NM_000518.4:c.51delC
NM_000518.5:c.51delCMANE SELECT
p.Lys18fs

Protein change:

K18fs

Links:

Genetic Testing Registry (GTR): GTR000500319; HBVAR: 799; OMIM: 141900.0323; dbSNP: rs35662066

NCBI 1000 Genomes Browser:

rs35662066

Molecular consequence:

NM_000518.5:c.51del - 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
SCV000697137	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Oct 31, 2016)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 6714226, 18294253, 19254853, 12368169, 22239493, 22392582, 12779277, 12403498, 18954999 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000697137

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Oct 31, 2016)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

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

Molecular characterization of seven beta-thalassemia mutations in Asian Indians.

Kazazian HH Jr, Orkin SH, Antonarakis SE, Sexton JP, Boehm CD, Goff SC, Waber PG.

EMBO J. 1984 Mar;3(3):593-6.

PubMed [citation]

PMID:: 6714226
PMCID:: PMC557393

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 (9)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697137.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

Variant summary: The HBB c.51delC (p.Lys18Argfs) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.85dupC, c.135delC). Mutation taster predicts a damaging outcome for this variant. This variant was found in 4/121395 control chromosomes at a frequency of 0.000033, which does not exceed the estimated maximal expected allele frequency of a pathogenic HBB variant (0.0111803). It was reported in several BTHAL patients some of whom were homologous for the variant indicating causality. 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 3, 2024

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