ClinVar Genomic variation as it relates to human health
NM_000458.4(HNF1B):c.244G>A (p.Asp82Asn)
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.
Uncertain significance(7); Benign(2); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000458.4(HNF1B):c.244G>A (p.Asp82Asn)
Variation ID: 193101 Accession: VCV000193101.56
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q12 17: 37744641 (GRCh38) [ NCBI UCSC ] 17: 36104632 (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 Dec 6, 2016 Jun 17, 2024 Feb 16, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000458.4:c.244G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000449.1:p.Asp82Asn missense NM_001165923.4:c.244G>A NP_001159395.1:p.Asp82Asn missense NM_001304286.2:c.244G>A NP_001291215.1:p.Asp82Asn missense NC_000017.11:g.37744641C>T NC_000017.10:g.36104632C>T NG_013019.2:g.5466G>A - Protein change
- D82N
- Other names
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- Canonical SPDI
- NC_000017.11:37744640: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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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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HNF1B | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
611 | 824 |
Conditions - Germline
Condition
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Dec 30, 2019 | RCV000173137.10 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jul 6, 2019 | RCV000314789.9 | |
Conflicting interpretations of pathogenicity (7) |
criteria provided, conflicting classifications
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Jan 18, 2024 | RCV000724384.24 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 11, 2019 | RCV001174365.2 | |
HNF1B-related disorder
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Uncertain significance (1) |
criteria provided, single submitter
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Feb 16, 2024 | RCV003937545.1 |
Uncertain significance (1) |
no assertion criteria provided
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Sep 1, 2021 | RCV001844814.1 | |
Likely benign (1) |
criteria provided, single submitter
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Dec 20, 2018 | RCV002444693.2 |
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
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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
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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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Uncertain significance
(Oct 27, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000539309.1
First in ClinVar: Dec 10, 2016 Last updated: Dec 10, 2016 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant is classified in HGMD as DM, related to HNF1B-related disease (reported in one patient, phenotype not specified). This variant is classified in ClinVar with 1 star as VUS by Emory. It is present in ExAC with a Max MAF of 0.12%. (less)
Method: Genome/Exome Filtration
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Uncertain significance
(Jul 06, 2019)
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criteria provided, single submitter
Method: literature only
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Renal cysts and diabetes syndrome
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg
Accession: SCV000926171.1
First in ClinVar: Jul 14, 2019 Last updated: Jul 14, 2019
Comment:
This variant and it's classification has been reported by Vasileiou et al. 2019; DOI:10.1101/576918. The variants has previously been reported in PMID:24897035 as "c.244 G>A … (more)
This variant and it's classification has been reported by Vasileiou et al. 2019; DOI:10.1101/576918. The variants has previously been reported in PMID:24897035 as "c.244 G>A p.Asp82Asn" with clinical significance Pathogenic. It has been re-classified using InterVar and manual curation as Uncertain significance based on PM1 PP3 PP5 BP6. (less)
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Uncertain significance
(Mar 15, 2018)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000224226.5
First in ClinVar: Jun 29, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 9
Sex: mixed
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Benign
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Renal cysts and diabetes syndrome
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000402434.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Benign
(Dec 30, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics
Accession: SCV001475669.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
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Uncertain significance
(Jan 05, 2023)
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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: SCV001824843.3
First in ClinVar: Sep 08, 2021 Last updated: Jan 21, 2023 |
Comment:
Reported in unrelated patients in published literature, including one individual with hyperuricemia, bilateral renal cysts and dysplasia, and stage 1 chronic kidney disease (Okorn et … (more)
Reported in unrelated patients in published literature, including one individual with hyperuricemia, bilateral renal cysts and dysplasia, and stage 1 chronic kidney disease (Okorn et al., 2019) and an individual whose clinical information was not provided (Yu et al., 2019); 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: 19639018, 26899772, 24897035, 27634015, 31264968, 30666461, 34426522, 32041611) (less)
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Uncertain significance
(Oct 21, 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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Revvity Omics, Revvity
Accession: SCV003808684.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Likely benign
(Jan 18, 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: SCV002431991.3
First in ClinVar: Apr 08, 2022 Last updated: Feb 20, 2024 |
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Likely benign
(Dec 20, 2018)
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criteria provided, single submitter
Method: clinical testing
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Maturity onset diabetes mellitus in young
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002732084.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Uncertain significance
(Jan 11, 2019)
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criteria provided, single submitter
Method: research
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Monogenic diabetes
Affected status: unknown
Allele origin:
unknown
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Personalized Diabetes Medicine Program, University of Maryland School of Medicine
Accession: SCV001337503.1
First in ClinVar: Jun 14, 2020 Last updated: Jun 14, 2020 |
Comment:
ACMG criteria: PP3 (REVEL 0.890 + 7 predictors); PP4 (19639018, 26899772; variant also identified in patient in PMID: 24897035 (no clinical info, can't tell if … (more)
ACMG criteria: PP3 (REVEL 0.890 + 7 predictors); PP4 (19639018, 26899772; variant also identified in patient in PMID: 24897035 (no clinical info, can't tell if overlap with other papers); BS2 (12 cases and 15 controls in T2Dgenes); BS1 (MAF in gnomAD EurNF population is 0.09%; 0.14% in ESP European pop)= scores as benign, but going to call as VUS given case reports and predictors (conflicting evidence). (less)
Number of individuals with the variant: 1
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Uncertain significance
(Feb 16, 2024)
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criteria provided, single submitter
Method: clinical testing
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HNF1B-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004747536.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The HNF1B c.244G>A variant is predicted to result in the amino acid substitution p.Asp82Asn. This variant has been reported in patients with HNF1B-related disease but … (more)
The HNF1B c.244G>A variant is predicted to result in the amino acid substitution p.Asp82Asn. This variant has been reported in patients with HNF1B-related disease but its pathogenicity was not conclusive (Faguer et al. 2014. PubMed ID: 24897035; Brahm et al. 2016. PubMed ID: 27634015; Yu et al. 2019. PubMed ID: 31264968, supplementary table 6; Okorn et al. 2019. PubMed ID: 30666461; Kanda et al. 2016. PubMed ID: 26899772; Zuber et al. 2009. PubMed ID: 19639018). This variant is reported in 0.11% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
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Likely benign
(Mar 01, 2022)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004144497.6
First in ClinVar: Nov 20, 2023 Last updated: Jun 17, 2024 |
Comment:
HNF1B: BS1:Supporting, BS2
Number of individuals with the variant: 1
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Uncertain significance
(Sep 01, 2021)
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no assertion criteria provided
Method: research
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Autosomal dominant polycystic liver disease
Affected status: yes
Allele origin:
germline
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Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center
Accession: SCV001877065.1
First in ClinVar: Mar 19, 2022 Last updated: Mar 19, 2022 |
Sex: female
Geographic origin: Netherlands
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001926999.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001798926.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 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 |
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New-onset diabetes after renal transplantation in a patient with a novel HNF1B mutation. | Kanda S | Pediatric transplantation | 2016 | PMID: 26899772 |
The HNF1B score is a simple tool to select patients for HNF1B gene analysis. | Faguer S | Kidney international | 2014 | PMID: 24897035 |
HNF1B-related diabetes triggered by renal transplantation. | Zuber J | Nature reviews. Nephrology | 2009 | PMID: 19639018 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=HNF1B | - | - | - | - |
- | - | - | - | DOI: 10.1101/576918 |
Text-mined citations for this variant ...
HelpRecord last updated Jun 17, 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.