ClinVar Genomic variation as it relates to human health
NM_006361.6(HOXB13):c.251G>A (p.Gly84Glu)
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.
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(11); Likely pathogenic(7); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_006361.6(HOXB13):c.251G>A (p.Gly84Glu)
Variation ID: 128031 Accession: VCV000128031.67
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.32 17: 48728343 (GRCh38) [ NCBI UCSC ] 17: 46805705 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Mar 20, 2016 Apr 15, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_006361.6:c.251G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006352.2:p.Gly84Glu missense NC_000017.11:g.48728343C>T NC_000017.10:g.46805705C>T NG_033789.1:g.5407G>A LRG_771:g.5407G>A LRG_771t1:c.251G>A LRG_771p1:p.Gly84Glu Q92826:p.Gly84Glu - Protein change
- G84E
- Other names
- p.G84E:GGA>GAA
- Canonical SPDI
- NC_000017.11:48728342:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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0.00020 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00099
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00154
The Genome Aggregation Database (gnomAD) 0.00160
The Genome Aggregation Database (gnomAD), exomes 0.00184
Exome Aggregation Consortium (ExAC) 0.00218
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 | ||
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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. |
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HOXB13 | - | - |
GRCh38 GRCh37 |
1674 | 1686 |
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. |
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Pathogenic (1) |
criteria provided, single submitter
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Nov 20, 2015 | RCV000210093.6 | |
Pathogenic/Likely pathogenic; association (12) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV000229815.46 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Oct 11, 2022 | RCV000561749.10 | |
Pathogenic/Likely pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Oct 30, 2023 | RCV000714291.16 | |
Likely pathogenic (1) |
no assertion criteria provided
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Mar 4, 2021 | RCV001391199.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 23, 2021 | RCV001582580.4 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Apr 26, 2023 | RCV003492500.1 | |
Pathogenic (1) |
criteria provided, single submitter
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- | RCV003335104.1 | |
Pathogenic (1) |
criteria provided, single submitter
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- | RCV003335105.1 |
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. |
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Pathogenic
(Nov 20, 2015)
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criteria provided, single submitter
Method: clinical testing
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Prostate cancer susceptibility
Affected status: no
Allele origin:
germline
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University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV000266072.1
First in ClinVar: Mar 20, 2016 Last updated: Mar 20, 2016 |
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
ovarian cancer (present)
Age: 60-69 years
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
breast cancer (present)
Age: 40-49 years
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
breast cancer (present)
Age: 40-49 years
Observation 4:
Number of individuals with the variant: 1
Clinical Features:
breast cancer (present)
Age: 40-49 years
Observation 5:
Number of individuals with the variant: 1
Clinical Features:
colon cancer (present)
Age: 50-59 years
Observation 6:
Number of individuals with the variant: 1
Clinical Features:
breast cancer (present)
Age: 60-69 years
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Uncertain significance
(-)
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criteria provided, single submitter
Method: research
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Hereditary cancer-predisposing syndrome
Affected status: yes
Allele origin:
paternal
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Department of Pediatric Oncology, Hematology and Clinical Immunology, University Clinics Duesseldorf
Accession: SCV001482293.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
Family history: no
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Pathogenic
(Mar 25, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000149878.13
First in ClinVar: May 17, 2014 Last updated: Apr 17, 2019 |
Comment:
Case control studies report that this variant is associated with prostate cancer with odds ratios ranging from 3.25 to 4.51 (Shang 2013, Huang 2014, Karlsson … (more)
Case control studies report that this variant is associated with prostate cancer with odds ratios ranging from 3.25 to 4.51 (Shang 2013, Huang 2014, Karlsson 2014, Cai 2015, Nyberg 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23099437, 23541221, 26517352, 26108461, 22853031, 24310616, 26638190, 27424772, 27625331, 30665703, 28265568, 25595936, 24148311, 23393222, 23292082, 22841674, 23475555, 23064873, 22781434, 23104005, 25629170, 22714738, 26289772, 26779768, 27004541, 23457453, 27034017, 26604137, 24722062, 23129385, 23396964, 27294245, 26931741, 26671023, 26803986, 25111073, 24026887, 23518396, 22236224, 27153395, 27902461, 27819754, 28050579, 28798948, 28790484, 28657667, 29181843, 28272408, 28186998, 29259341, 29236593, 28598379, 28442163, 30527799, 31137568, 30560549, 31556563, 30777372, 31980526, 32546843, 31948886, 27626483, 31589614, 33504652, 32830201) (less)
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Pathogenic
(Jan 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV002522530.1
First in ClinVar: Jun 05, 2022 Last updated: Jun 05, 2022 |
Comment:
PP1_strong, PS4
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Pathogenic
(Sep 26, 2022)
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criteria provided, single submitter
Method: research
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Prostate cancer, hereditary, 9
Affected status: unknown
Allele origin:
unknown
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HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: COAGS
Accession: SCV002575021.1 First in ClinVar: Oct 01, 2022 Last updated: Oct 01, 2022 |
Comment:
PS4, PP1_Strong, PP3
Number of individuals with the variant: 1
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Likely pathogenic
(Aug 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Prostate cancer, hereditary, 9
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002580137.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
Number of individuals with the variant: 13
Sex: female
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Likely pathogenic
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002009557.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Likely pathogenic
(Oct 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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Prostate cancer, hereditary, 9
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004199911.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jun 25, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV002774349.2
First in ClinVar: Dec 31, 2022 Last updated: Jan 06, 2024 |
Comment:
In the published literature, this variant is reported to be significantly associated with an increased risk of prostate cancer, with higher risks observed for early-onset … (more)
In the published literature, this variant is reported to be significantly associated with an increased risk of prostate cancer, with higher risks observed for early-onset and familial disease compared with late-onset and sporadic disease (PMIDs: 23518396 (2013), 24026887 (2014), and 26517352 (2015)). In addition, this variant is reported to be a founder variant in European populations (PMIDs: 23064873 (2013) and 22841674 (2014)). Furthermore, this variant’s cumulative effects on HOXB13 protein function are inconclusive and require further investigation (PMID: 30560549 (2019)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is disease causing and damaging. Based on the available information, this variant is classified as pathogenic. (less)
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Likely pathogenic
(Apr 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV004240700.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
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association
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000289513.9
First in ClinVar: Jul 03, 2016 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 84 of the HOXB13 protein … (more)
This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 84 of the HOXB13 protein (p.Gly84Glu). This variant is present in population databases (rs138213197, gnomAD 0.8%), and has an allele count higher than expected for a pathogenic variant. Numerous family studies, population-based case-control studies, and large meta-analyses have shown that this variant confers an elevated risk for prostate cancer (PMID: 23064873, 22841674, 26517352, 23518396, 24026887). In a large meta-analysis involving 11 studies with ~120,000 cases and controls (PMID: 24026887), men carrying this variant had a 4.51-fold higher relative risk of prostate cancer compared with non-carriers (95 % CI 3.28-6.20). Higher risks were observed in individuals with early-onset disease (OR=9.73, 95% CI 6.57-14.39), more than two affected relatives (OR=7.27, 95 % CI 4.02-13.15), and highly aggressive disease (OR=5.81, 95% CI 3.72-9.08). ClinVar contains an entry for this variant (Variation ID: 128031). Both population studies and haplotype analyses suggest that this variant is a European founder mutation, explaining the higher frequency in these populations (PMID: 22841674, 23064873). ClinVar contains an entry for this variant (Variation ID: 128031). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt HOXB13 protein function with a negative predictive value of 80%. In summary, this is a common variant that is associated with an increased risk for developing disease. For these reasons, this variant has been classified as an Increased Risk Allele. (less)
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Pathogenic
(Jul 25, 2019)
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criteria provided, single submitter
Method: clinical testing
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Prostate cancer, hereditary, 9
Affected status: unknown
Allele origin:
unknown
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Illumina Laboratory Services, Illumina
Accession: SCV001451564.1
First in ClinVar: Dec 23, 2020 Last updated: Dec 23, 2020 |
Comment:
The HOXB13 c.251G>A (p.Gly84Glu) variant is a missense variant that has been associated with an increased risk of prostate cancer. Ewing et al. (2012) first … (more)
The HOXB13 c.251G>A (p.Gly84Glu) variant is a missense variant that has been associated with an increased risk of prostate cancer. Ewing et al. (2012) first identified the p.Gly84Glu variant in a heterozygous state in 18 men from four families with familial prostate cancer. Subsequent large case-control studies and two meta-analysis studies demonstrated that the p.Gly84Glu variant was associated with a significantly increased prostate cancer susceptibility in variant carriers compared with non-carriers, with odds ratios ranging from 3.38-4.51, and was also significantly associated with early-onset, positive family history, and highly aggressive disease (Huang et al. 2014; Zhang et al. 2016). Carriers of the p.Gly84Glu variant were estimated to have a 33-60% lifetime risk of prostate cancer compared to the general population risk of 12% (Karlsson et al. 2014; Hoffman et al. 2015). The p.Gly84Glu variant is reported at a frequency of 0.007618 in the European (Finnish) population of the Genome Aggregation Database and has been identified as a founder variant in European ancestry (Xu et al. 2013). Based on the collective evidence and application of ACMG criteria, the p.Gly84Glu variant is classified as pathogenic for prostate cancer susceptibility. (less)
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Pathogenic
(Aug 23, 2021)
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criteria provided, single submitter
Method: clinical testing
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Familial prostate carcinoma
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001821360.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
Variant summary: HOXB13 c.251G>A (p.Gly84Glu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging … (more)
Variant summary: HOXB13 c.251G>A (p.Gly84Glu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0018 in 249538 control chromosomes in the gnomAD database, including 2 homozygotes. c.251G>A has been reported in the literature in multiple individuals affected with Prostate Cancer, which include segregation in multiple families, and several studies have reported the variant as a European founder mutation. Family studies, population-based case-control studies, and large meta-analyses have shown the variant to confer an elevated risk for prostate cancer (eg. Huang_2014, Cai_2015, Ewing_2012). For example, a meta-analyses of 11 studies including 120,167 participants reported that men with the HOXB13 G84E variant had a 4.51-fold higher relative risk of prostate cancer compared with non-carriers (95 % CI 3.28-6.20; Huang_2014). The much higher risks were observed in individuals with early onset (odds ratio (OR)=9.73, 95 % confidence interval 6.57-14.39), more than two affected relatives (OR=7.27, 95 % CI 4.02-13.15), and highly aggressive disease (OR=5.81, 95 % CI 3.72-9.08). Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(May 04, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Prostate cancer, hereditary, 9
Affected status: unknown
Allele origin:
germline
|
Mendelics
Accession: SCV002516559.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
|
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Likely pathogenic
(Oct 11, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000664774.4
First in ClinVar: Jan 01, 2018 Last updated: Nov 29, 2022 |
Comment:
The p.G84E variant (also known as c.251G>A), located in coding exon 1 of the HOXB13 gene, results from a G to A substitution at nucleotide … (more)
The p.G84E variant (also known as c.251G>A), located in coding exon 1 of the HOXB13 gene, results from a G to A substitution at nucleotide position 251. The glycine at codon 84 is replaced by glutamic acid, an amino acid with similar properties. This alteration is located in a highly conserved region of HOXB13 that plays an important role in mediating the binding of HOX13 paralogues to the MEIS family of HOX cofactor proteins (Ewing CM et al. N. Engl. J. Med. 2012 Jan;366:141-9). Several large case-control studies have shown an association of the p.G84E alteration with increased prostate cancer risk (Ewing CM et al. N. Engl. J. Med. 2012 Jan;366:141-9; Breyer JP et al. Cancer Epidemiol. Biomarkers Prev. 2012 Aug;21:1348-53; Akbari MR et al. J. Natl. Cancer Inst. 2012 Aug;104:1260-2; Xu J et al. Hum. Genet. 2013 Jan;132:5-14; Karlsson R et al. Eur. Urol. 2014 Jan;65:169-76; Hoffmann TJ et al. PLoS Genet. 2015 Jan;11:e1004930; Karyadi DM et al. Oncotarget. 2017 Jan;8:1495-1507). Meta-analyses have estimated that male carriers of the p.G84E alteration have an approximate 2.8 to 4-fold risk of prostate cancer compared to the general population; however, exact lifetime risk figures are not currently available (Shang Z et al. Eur. Urol. 2013 Jul;64:173-6; Huang H et al. Tumour Biol. 2014 Feb;35:1177-82; Cai Q et al. Oncotarget. 2015 Dec;6:42312-21; Nyberg T et al. Eur. Urol. 2019 05;75(5):834-845). Of note, this alteration has been reported predominantly in individuals of European descent, and is estimated to contribute to up to 5% of high-risk prostate cancer families in this population (Xu J et al. Hum. Genet. 2013 Jan;132:5-14). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
Number of individuals with the variant: 1
|
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Pathogenic
(Nov 25, 2021)
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criteria provided, single submitter
Method: clinical testing
|
Prostate cancer, hereditary, 9
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556661.2
First in ClinVar: Aug 04, 2022 Last updated: Dec 17, 2022 |
|
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Likely pathogenic
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004026833.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
|
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
|
HOXB13-related disorders
Affected status: yes
Allele origin:
germline
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Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV004046272.1
First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023 |
Comment:
This variant has been previously associated with increased risk for prostate cancer, breast cancer, colorectal cancer, bladder cancer, and leukemia (PMID: 22236224, 22853031, 23541221, 26108461, … (more)
This variant has been previously associated with increased risk for prostate cancer, breast cancer, colorectal cancer, bladder cancer, and leukemia (PMID: 22236224, 22853031, 23541221, 26108461, 26108461). Large prostate cancer case-control meta-analysis studies of this variant have reported odds ratios of 3.25-4.51 for prostate cancer (PMID: 22841674, 23518396, 24026887). Higher odds ratios were observed for early-onset, familial, and highly aggressive prostate cancer (PMID: 24026887). This variant has been reported to segregate with prostate cancer in multiple families (PMID: 22236224). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.19% (528/280842) across all populations and at a frequency of 0.76% (191/25072) in the European Finnish population, suggesting that this variant is a founder mutation in this population. The c.251G>A (p.Gly84Glu) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.251G>A (p.Gly84Glu) variant is classified as Pathogenic. (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
|
HOXB13-Related Cancer Predisposition
Affected status: yes
Allele origin:
germline
|
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV004046400.1
First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023 |
Comment:
This variant has been previously associated with increased risk for prostate cancer, colorectal cancer, bladder cancer, and leukemia (PMID: 22236224, 23541221, 26108461). Large prostate cancer … (more)
This variant has been previously associated with increased risk for prostate cancer, colorectal cancer, bladder cancer, and leukemia (PMID: 22236224, 23541221, 26108461). Large prostate cancer case-control meta-analysis studies of this variant have reported odds ratios of 3.25-4.51 for prostate cancer (PMID: 22841674, 23518396, 24026887). Higher odds ratios were observed for early-onset, familial, and highly aggressive prostate cancer (PMID: 24026887). This variant has been reported to segregate with prostate cancer in multiple families (PMID: 22236224). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.19% (528/280842) across all populations and at a frequency of 0.76% (191/25072) in the European Finnish population, suggesting that this variant is a founder mutation in this population. The c.251G>A (p.Gly84Glu) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.251G>A (p.Gly84Glu) variant is classified as Pathogenic. (less)
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Likely pathogenic
(Oct 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV000892224.22
First in ClinVar: Mar 31, 2019 Last updated: Apr 15, 2024 |
Comment:
HOXB13: PS4, PM1, PP3
Number of individuals with the variant: 14
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Pathogenic
(Oct 23, 2018)
|
no assertion criteria provided
Method: literature only
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PROSTATE CANCER, HEREDITARY, 9
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000844980.1
First in ClinVar: Oct 29, 2018 Last updated: Oct 29, 2018 |
Comment on evidence:
To identify a prostate cancer susceptibility gene in the 17q21-q22 region (HPC9; 610997), Ewing et al. (2012) sequenced 2,009 exons from 202 genes in germline … (more)
To identify a prostate cancer susceptibility gene in the 17q21-q22 region (HPC9; 610997), Ewing et al. (2012) sequenced 2,009 exons from 202 genes in germline DNA from 94 unrelated patients with prostate cancer from families selected for linkage to the candidate region. They then tested family members, additional case subjects, and control subjects to characterize the frequency of the identified mutations. Probands from 4 families were discovered to have a rare but recurrent mutation, G84E (rs138213197), in HOXB13. All 18 men with prostate cancer and available DNA in these 4 families carried the mutation. At the time of the analysis the G84E mutation was not reported in dbSNP or in the NCBI 1000 Genomes sequencing project (May 2011), which included 1,094 subjects, 381 of European descent. The carrier rate of the G84E mutation was increased by a factor of approximately 20 in 5,083 unrelated subjects of European descent who had prostate cancer, with the mutation found in 72 subjects (1.4%), as compared with 1 in 1,401 control subjects (0.1%) (P = 8.5 x 10(-7)). The mutation was significantly more common in men with early-onset, familial prostate cancer (3.1%) than in those with late-onset, nonfamilial prostate cancer (0.6%) (P = 2.0 x 10(-6)). Hamosh (2018) noted that the G84E mutation in the HOXB13 gene was present in 530 of 275,718 alleles and in 2 homozygotes in the gnomAD database (October 23, 2018). (less)
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Likely pathogenic
(Mar 04, 2021)
|
no assertion criteria provided
Method: case-control
|
Carcinoma of pancreas
Affected status: yes
Allele origin:
germline
|
CZECANCA consortium
Accession: SCV001593142.1
First in ClinVar: May 14, 2021 Last updated: May 14, 2021 |
Number of individuals with the variant: 1
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
|
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001743393.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
|
Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799539.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808755.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
|
|
Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001957343.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001974877.2 First in ClinVar: Oct 07, 2021 Last updated: Oct 16, 2021 |
|
|
Uncertain significance
(Jun 24, 2021)
|
no assertion criteria provided
Method: clinical testing
|
Prostate cancer, hereditary, 9
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, University Hospital Schleswig-Holstein
Accession: SCV002011756.1
First in ClinVar: Nov 06, 2021 Last updated: Nov 06, 2021 |
|
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk. | Liu J | Scientific reports | 2020 | PMID: 32546843 |
HOXB13 interaction with MEIS1 modifies proliferation and gene expression in prostate cancer. | Johng D | The Prostate | 2019 | PMID: 30560549 |
Homeobox B13 G84E Mutation and Prostate Cancer Risk. | Nyberg T | European urology | 2019 | PMID: 30527799 |
HOXB13 mutations and binding partners in prostate development and cancer: Function, clinical significance, and future directions. | Brechka H | Genes & diseases | 2017 | PMID: 28798948 |
Whole exome sequencing in 75 high-risk families with validation and replication in independent case-control studies identifies TANGO2, OR5H14, and CHAD as new prostate cancer susceptibility genes. | Karyadi DM | Oncotarget | 2017 | PMID: 27902461 |
Oncogenic mechanisms of HOXB13 missense mutations in prostate carcinogenesis. | Cardoso M | Oncoscience | 2016 | PMID: 28050579 |
Association between germline homeobox B13 (HOXB13) G84E allele and prostate cancer susceptibility: a meta-analysis and trial sequential analysis. | Zhang J | Oncotarget | 2016 | PMID: 27626483 |
Recurrent HOXB13 mutations in the Dutch population do not associate with increased breast cancer risk. | Liu J | Scientific reports | 2016 | PMID: 27424772 |
Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. | Maxwell KN | American journal of human genetics | 2016 | PMID: 27153395 |
Dysregulation of the homeobox transcription factor gene HOXB13: role in prostate cancer. | Decker B | Pharmacogenomics and personalized medicine | 2014 | PMID: 25206306 |
HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG). | Xu J | Human genetics | 2013 | PMID: 23064873 |
Association of a HOXB13 variant with breast cancer. | Alanee S | The New England journal of medicine | 2012 | PMID: 22853031 |
Germline mutations in HOXB13 and prostate-cancer risk. | Ewing CM | The New England journal of medicine | 2012 | PMID: 22236224 |
Posterior Hox gene expression and differential androgen regulation in the developing and adult rat prostate lobes. | Huang L | Endocrinology | 2007 | PMID: 17138648 |
Hoxb13 up-regulates transglutaminase activity and drives terminal differentiation in an epidermal organotypic model. | Mack JA | The Journal of biological chemistry | 2005 | PMID: 15964834 |
Hoxb-13: a new Hox gene in a distant region of the HOXB cluster maintains colinearity. | Zeltser L | Development (Cambridge, England) | 1996 | PMID: 8756292 |
Hamosh, A. Personal Communication. 2018. Baltimore, Md. | - | - | - | - |
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Text-mined citations for rs138213197 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.