NM_000518.5(HBB):c.323dup (p.Asn109fs) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Mar 1, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000506185.3

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)

Identifiers:
MedGen: CN517202

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
SCV000601289Quest Diagnostics Nichols Institute San Juan Capistranocriteria provided, single submitter
Pathogenic
(Jun 30, 2017)
germlineclinical testing

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

SCV001384504Invitaecriteria provided, single submitter
Likely pathogenic
(Mar 1, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317
See all PubMed Citations (11)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601289.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001384504.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change results in a premature translational stop signal in the HBB gene (p.Asn109Glnfs*32). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 39 amino acids of the HBB protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with thalassemia (PMID: 3683554, 9401495, 1897518, 1728311). This is also known as 106/107(+G) in the literature. ClinVar contains an entry for this variant (Variation ID: 439153). This variant disrupts the p.Glu122 amino acid residue in HBB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25666204, 24616059, 24245819, 2895770). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Aug 27, 2021

Support Center