VCV000015422.128 - ClinVar

NM_000518.5(HBB):c.17_18del (p.Pro6fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(18)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000518.5(HBB):c.17_18del (p.Pro6fs)

Variation ID: 15422 Accession: VCV000015422.128

Type and length

Deletion, 2 bp

Location

Cytogenetic: 11p15.4 11: 5227004-5227005 (GRCh38) [ NCBI UCSC ] 11: 5248234-5248235 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Sep 30, 2017	Oct 20, 2024	Jul 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000518.5:c.17_18del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000509.1:p.Pro6fs	frameshift
NM_000518.5:c.17_18delCT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NC_000011.10:g.5227004_5227005del
NC_000011.9:g.5248234_5248235del
NG_000007.3:g.70611_70612del
NG_042296.1:g.535_536del
NG_046672.1:g.4939_4940del
NG_059281.1:g.5067_5068del
LRG_1232:g.5067_5068del
LRG_1232t1:c.17_18del	LRG_1232p1:p.Pro6fs

... more HGVS ... less HGVS

Protein change

P6fs

Other names

CD 5 -CT

Canonical SPDI

NC_000011.10:5227003:AG:

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00000

Exome Aggregation Consortium (ExAC) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00004

Links

Genetic Testing Registry (GTR): GTR000500319 Genetic Testing Registry (GTR): GTR000556525 OMIM: 141900.0332 dbSNP: rs34889882 HBVAR: 783 ClinGen: CA125288 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
HBB		-	-	GRCh38 GRCh37	22	1835
LOC106099062	-	-	-	GRCh38	-	863
LOC107133510	-	-	-	GRCh38	-	1785

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Beta zero thalassemia	Pathogenic (1)	no assertion criteria provided	Jan 1, 1989	RCV000016678.36
beta Thalassemia	Pathogenic (6)	criteria provided, multiple submitters, no conflicts	Nov 3, 2022	RCV000586913.17
not provided	Pathogenic (6)	criteria provided, multiple submitters, no conflicts	Jul 31, 2024	RCV000506399.49
Hb SS disease	Pathogenic (1)	criteria provided, single submitter	-	RCV001004360.9
HBB-related disorder	Pathogenic (1)	no assertion criteria provided	Feb 11, 2024	RCV004541006.2
Beta-thalassemia HBB/LCRB Dominant beta-thalassemia Erythrocytosis, familial, 6 Hb SS disease Heinz body anemia Hereditary persistence of fetal hemoglobin METHEMOGLOBINEMIA, BETA TYPE Malaria, susceptibility to alpha Thalassemia	Pathogenic (1)	criteria provided, single submitter	Jul 12, 2021	RCV002476977.8
Beta-thalassemia HBB/LCRB	Pathogenic (2)	criteria provided, single submitter	Feb 1, 2024	RCV004566747.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (May 08, 2018)	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018)) Method: clinical testing	Beta-thalassemia HBB/LCRB Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000799824.1 First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018	Publications: PubMed (4) PubMed: 24052702‚ 15278762‚ 25617386‚ 2606727
Pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hb SS disease Affected status: unknown Allele origin: germline	Baylor Genetics Accession: SCV001163298.1 First in ClinVar: Feb 29, 2020 Last updated: Feb 29, 2020
Pathogenic (Jan 05, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics and Genomics, Karolinska University Hospital Accession: SCV001450168.1 First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020	Number of individuals with the variant: 7
Pathogenic (Jul 12, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Heinz body anemia Hereditary persistence of fetal hemoglobin Dominant beta-thalassemia Hb SS disease alpha Thalassemia Malaria, susceptibility to Beta-thalassemia HBB/LCRB METHEMOGLOBINEMIA, BETA TYPE Erythrocytosis, familial, 6 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV001752822.2 First in ClinVar: Jul 18, 2021 Last updated: Dec 31, 2022
Pathogenic (May 22, 2023)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000601252.3 First in ClinVar: Sep 30, 2017 Last updated: Jan 06, 2024	Publications: PubMed (5) PubMed: 33491330‚ 25617386‚ 2606727‚ 27263053‚ 23457306 Comment: The HBB c.17_18del (p.Pro6Argfs17) variant (also known as CD5 (-CT)) alters the translational reading frame of the HBB mRNA and causes the premature termination of … (more) The HBB c.17_18del (p.Pro6Argfs17) variant (also known as CD5 (-CT)) alters the translational reading frame of the HBB mRNA and causes the premature termination of HBB protein synthesis. In the published literature, this variant has been reported in the compound heterozygous and homozygous state in individuals with beta-thalassemia major and intermedia (PMIDs: 33491330 (2021), 27263053 (2016), 25617386 (2015), 2606727 (1989)). Based on the available information, this variant is classified as pathogenic. (less)
Pathogenic (Dec 30, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001215748.5 First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024	Publications: PubMed (2) PubMed: 23637309‚ 2606727 Comment: This sequence change creates a premature translational stop signal (p.Pro6Argfs17) in the HBB gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Pro6Argfs17) in the HBB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HBB are known to be pathogenic (PMID: 23637309). This variant is present in population databases (rs34889882, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with beta thalassemia (PMID: 2606727). This variant is also known as Pro5fs and FSC-5(-CT). ClinVar contains an entry for this variant (Variation ID: 15422). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Nov 15, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV001160085.8 First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024	Comment: The HBB c.17_18delCT; p.Pro6ArgfsTer17 variant (rs34889882, HbVarID: 783), also known as Codon 5 (-CT) or Pro5fs when numbered from the mature protein, has been reported … (more) The HBB c.17_18delCT; p.Pro6ArgfsTer17 variant (rs34889882, HbVarID: 783), also known as Codon 5 (-CT) or Pro5fs when numbered from the mature protein, has been reported in the literature in an individual with beta(0) thalassemia (Kollia 1989, HbVar database and references therein). This variant is reported as pathogenic in ClinVar (Variation ID: 15422). It is found in the general population with an overall allele frequency of 0.004% (11/251156 alleles) in the Genome Aggregation Database. This variant causes a frameshift by deleting 2 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Kollia et al. Frameshift codon 5 (Fsc-5 (-CT)) thalassemia; a novel mutation detected in a Greek patient. Hemoglobin. 1989;13(6):597-604. PMID: 2606727. (less)
Pathogenic (Nov 03, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	beta Thalassemia Affected status: unknown Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV004847531.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024	Comment: The p.Pro6ArgfsX17 variant in HBB has been reported in several individuals with beta thalassemia and is one of the common pathogenic variants in Middle Eastern … (more) The p.Pro6ArgfsX17 variant in HBB has been reported in several individuals with beta thalassemia and is one of the common pathogenic variants in Middle Eastern countries ( selected references Kollia 1989 PMID: 2606727, Vetter 1997 PMID: 9163586, Murad 2021 PMID: 33491330). It has also been reported in ClinVar (Variation ID 15422) and was identified in 6/4834 South Asian chromosomes by gnomAD (https://gnomad.broadinstitute.org). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 6 and leads to a premature termination codon 17 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the HBB gene is an established disease mechanism in autosomal recessive beta thalassemia. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive beta thalassemia. ACMG/AMP Criteria applied: PM2_Supporting, PVS1, PM3_Strong. (less)
Pathogenic (Feb 01, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: curation	Beta-thalassemia HBB/LCRB Affected status: no Allele origin: germline	Laboratory of Medical Genetics, National & Kapodistrian University of Athens Accession: SCV005051815.1 First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024
Pathogenic (Jul 31, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV005090883.1 First in ClinVar: Aug 04, 2024 Last updated: Aug 04, 2024
Pathogenic (Jun 06, 2017)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	beta Thalassemia Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000697089.1 First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018	Publications: PubMed (5) PubMed: 15278762‚ 2606727‚ 17486505‚ 25617386‚ 9225979 Comment: Variant summary: The HBB c.17_18delCT is a frame-shift variant resulting in termination of translation at codon 23, which is predicted to cause either a truncated … (more) Variant summary: The HBB c.17_18delCT is a frame-shift variant resulting in termination of translation at codon 23, which is predicted to cause either a truncated or absent HBB protein through non-sense mediated decay which is a commonly known mechanism for BTHAL. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Leu29fs). This variant is found in 1/121340 control chromosomes from ExAC at a frequency of 0.0000082, which does not exceed the maximal expected frequency of a pathogenic allele (0.0111803) in this gene. This variant has been commonly identified in beta-thalassemia patients in both compound heterozygous and homozygous states. It is also reported as one of the common mutations in Middle Eastern countries (Lahiry_2008). Taken together, this variant has been classified as a disease variant/pathogenic. (less)
Pathogenic (Jul 22, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Beta-thalassemia HBB/LCRB Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001810474.1 First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021	Sex: mixed
Pathogenic (Aug 01, 2021)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001500949.23 First in ClinVar: Mar 14, 2021 Last updated: Oct 20, 2024	Number of individuals with the variant: 2
Pathogenic (Jan 01, 1989)	no assertion criteria provided Method: literature only	BETA-ZERO-THALASSEMIA Affected status: not provided Allele origin: germline	OMIM Accession: SCV000036948.2 First in ClinVar: Apr 04, 2013 Last updated: May 09, 2018	Publications: PubMed (1) PubMed: 2606727 Comment on evidence: Frameshift, -CT, codon 5, CCT to CC, was found in a Mediterranean patient by Kollia et al. (1989).
Pathogenic (May 07, 2024)	no assertion criteria provided Method: clinical testing	Beta-thalassemia HBB/LCRB Affected status: yes Allele origin: germline	MOLECULAR BIOLOGY AND HUMAN GENETICS DIVISION, THE UNIVERSITY OF BURDWAN Accession: SCV005186160.1 First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024	Publications: PubMed (1) PubMed: 33491330 Comment: The HBB c.17_18delCT (NP_000509.1:p.Pro6fs ) is a frame-shift variant, which is also a beta 0 mutation. When this variant present with other pathogenic HBB mutation … (more) The HBB c.17_18delCT (NP_000509.1:p.Pro6fs ) is a frame-shift variant, which is also a beta 0 mutation. When this variant present with other pathogenic HBB mutation leads to severe type of thalassemia. Patients needing blood transfusion, often presented with hepatosplenomegaly, Iron overload. The frequency of the variant among thalassemia patient in Eastern India is 0.19 % as per our multicentric project - A Genetic Diagnostic Algorithm Based Study for Thalassemia in Northern and Eastern Indian Populations, Funded by Dept. of Biotechnology , Govt of India [Project No. BT/PR26461/MED/12/821/2018] (less) Number of individuals with the variant: 1 Sex: female Ethnicity/Population group: Southeast Asian Geographic origin: India
Pathogenic (Feb 11, 2024)	no assertion criteria provided Method: clinical testing	HBB-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004793003.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: The HBB c.17_18delCT variant is predicted to result in a frameshift and premature protein termination (p.Pro6Argfs17). This variant is also known as Codon 5 [-CT], … (more) The HBB c.17_18delCT variant is predicted to result in a frameshift and premature protein termination (p.Pro6Argfs17). This variant is also known as Codon 5 [-CT], FSC-5(-CT), or CD 5 -CT in the literature. This variant was reported in the homozygous and compound heterozygous states to be causative for autosomal recessive beta-thalassemia (Kollia et al. 1989. PubMed ID: 2606727; Elmezayen et al. 2015. PubMed ID: 25617386; Murad et al. 2021. PubMed ID: 33491330). This variant is reported in 0.036% of alleles in individuals of South Asian descent in gnomAD. Frameshift variants in HBB are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
Pathogenic (Nov 25, 2019)	no assertion criteria provided Method: curation	beta Thalassemia Affected status: unknown Allele origin: germline	The ITHANET community portal, The Cyprus Institute of Neurology and Genetics Accession: SCV001244626.1 First in ClinVar: May 04, 2020 Last updated: May 04, 2020	Publications: PubMed (2) PubMed: 2606727‚ 27263053 Other databases https://ithanet.eu/db/ithagenes?… https://ithanet.eu/db/ithagenes?ithaID=54
Pathogenic (Mar 17, 2017)	no assertion criteria provided Method: clinical testing	Beta thalassemia Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV002091615.1 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022
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Comment:

The HBB c.17_18del (p.Pro6Argfs*17) variant (also known as CD5 (-CT)) alters the translational reading frame of the HBB mRNA and causes the premature termination of HBB protein synthesis. In the published literature, this variant has been reported in the compound heterozygous and homozygous state in individuals with beta-thalassemia major and intermedia (PMIDs: 33491330 (2021), 27263053 (2016), 25617386 (2015), 2606727 (1989)). Based on the available information, this variant is classified as pathogenic.

Comment:

This sequence change creates a premature translational stop signal (p.Pro6Argfs*17) in the HBB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HBB are known to be pathogenic (PMID: 23637309). This variant is present in population databases (rs34889882, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with beta thalassemia (PMID: 2606727). This variant is also known as Pro5fs and FSC-5(-CT). ClinVar contains an entry for this variant (Variation ID: 15422). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

Comment:

The HBB c.17_18delCT; p.Pro6ArgfsTer17 variant (rs34889882, HbVarID: 783), also known as Codon 5 (-CT) or Pro5fs when numbered from the mature protein, has been reported in the literature in an individual with beta(0) thalassemia (Kollia 1989, HbVar database and references therein). This variant is reported as pathogenic in ClinVar (Variation ID: 15422). It is found in the general population with an overall allele frequency of 0.004% (11/251156 alleles) in the Genome Aggregation Database. This variant causes a frameshift by deleting 2 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Kollia et al. Frameshift codon 5 (Fsc-5 (-CT)) thalassemia; a novel mutation detected in a Greek patient. Hemoglobin. 1989;13(6):597-604. PMID: 2606727.

Comment:

The p.Pro6ArgfsX17 variant in HBB has been reported in several individuals with beta thalassemia and is one of the common pathogenic variants in Middle Eastern countries ( selected references Kollia 1989 PMID: 2606727, Vetter 1997 PMID: 9163586, Murad 2021 PMID: 33491330). It has also been reported in ClinVar (Variation ID 15422) and was identified in 6/4834 South Asian chromosomes by gnomAD (https://gnomad.broadinstitute.org). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 6 and leads to a premature termination codon 17 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the HBB gene is an established disease mechanism in autosomal recessive beta thalassemia. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive beta thalassemia. ACMG/AMP Criteria applied: PM2_Supporting, PVS1, PM3_Strong.

Comment:

Variant summary: The HBB c.17_18delCT is a frame-shift variant resulting in termination of translation at codon 23, which is predicted to cause either a truncated or absent HBB protein through non-sense mediated decay which is a commonly known mechanism for BTHAL. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Leu29fs). This variant is found in 1/121340 control chromosomes from ExAC at a frequency of 0.0000082, which does not exceed the maximal expected frequency of a pathogenic allele (0.0111803) in this gene. This variant has been commonly identified in beta-thalassemia patients in both compound heterozygous and homozygous states. It is also reported as one of the common mutations in Middle Eastern countries (Lahiry_2008). Taken together, this variant has been classified as a disease variant/pathogenic.

Comment:

The HBB c.17_18delCT (NP_000509.1:p.Pro6fs ) is a frame-shift variant, which is also a beta 0 mutation. When this variant present with other pathogenic HBB mutation leads to severe type of thalassemia. Patients needing blood transfusion, often presented with hepatosplenomegaly, Iron overload. The frequency of the variant among thalassemia patient in Eastern India is 0.19 % as per our multicentric project - A Genetic Diagnostic Algorithm Based Study for Thalassemia in Northern and Eastern Indian Populations, Funded by Dept. of Biotechnology , Govt of India [Project No. BT/PR26461/MED/12/821/2018]

Comment:

The HBB c.17_18delCT variant is predicted to result in a frameshift and premature protein termination (p.Pro6Argfs*17). This variant is also known as Codon 5 [-CT], FSC-5(-CT), or CD 5 -CT in the literature. This variant was reported in the homozygous and compound heterozygous states to be causative for autosomal recessive beta-thalassemia (Kollia et al. 1989. PubMed ID: 2606727; Elmezayen et al. 2015. PubMed ID: 25617386; Murad et al. 2021. PubMed ID: 33491330). This variant is reported in 0.036% of alleles in individuals of South Asian descent in gnomAD. Frameshift variants in HBB are expected to be pathogenic. This variant is interpreted as pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A rare gene variation cap +1 (A>C) (HBB: c. -50A>C) associated with codon 5 (-CT) (HBB: c.17_18delCT) mutation in Syrian family.	Murad H	Molecular genetics & genomic medicine	2021	PMID: 33491330
The molecular characterization of Beta globin gene in thalassemia patients reveals rare and a novel mutations in Pakistani population.	Yasmeen H	European journal of medical genetics	2016	PMID: 27263053
β-Globin Mutations in Egyptian Patients With β-Thalassemia.	Elmezayen AD	Laboratory medicine	2015	PMID: 25617386
The molecular basis of β-thalassemia.	Thein SL	Cold Spring Harbor perspectives in medicine	2013	PMID: 23637309
Self-catalytic DNA depurination underlies human β-globin gene mutations at codon 6 that cause anemias and thalassemias.	Alvarez-Dominguez JR	The Journal of biological chemistry	2013	PMID: 23457306
Molecular Genetic Characterization of β-Thalassemia and Sickle Cell Syndrome in the Albanian Population.	Babameto-Laku A	Balkan journal of medical genetics : BJMG	2011	PMID: 24052702
Molecular basis of beta-thalassemia and other hemoglobinopathies in Bulgaria: an update.	Petkov GH	Hemoglobin	2007	PMID: 17486505
Molecular genetic analyses of beta-thalassemia in South India reveals rare mutations in the beta-globin gene.	Bashyam MD	Journal of human genetics	2004	PMID: 15278762
Regional distribution of beta-thalassemia mutations in India.	Verma IC	Human genetics	1997	PMID: 9225979
Frameshift codon 5 [Fsc-5 (-CT)] thalassemia; a novel mutation detected in a Greek patient.	Kollia P	Hemoglobin	1989	PMID: 2606727
https://ithanet.eu/db/ithagenes?ithaID=54	-	-	-	-
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Text-mined citations for rs34889882 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 19, 2024

ClinVar Genomic variation as it relates to human health

NM_000518.5(HBB):c.17_18del (p.Pro6fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs34889882 ...