ClinVar Genomic variation as it relates to human health
NM_001277115.2(DNAH11):c.10472G>A (p.Arg3491His)
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(9); Benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001277115.2(DNAH11):c.10472G>A (p.Arg3491His)
Variation ID: 198347 Accession: VCV000198347.45
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7p15.3 7: 21816606 (GRCh38) [ NCBI UCSC ] 7: 21856224 (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 Apr 9, 2018 Apr 15, 2024 Jan 30, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001277115.2:c.10472G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001264044.1:p.Arg3491His missense NC_000007.14:g.21816606G>A NC_000007.13:g.21856224G>A NG_012886.2:g.278392G>A - Protein change
- R3491H
- Other names
- -
- Canonical SPDI
- NC_000007.14:21816605:G:A
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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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0.00100 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00048
Trans-Omics for Precision Medicine (TOPMed) 0.00055
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00065
The Genome Aggregation Database (gnomAD), exomes 0.00065
Exome Aggregation Consortium (ExAC) 0.00072
1000 Genomes Project 30x 0.00094
1000 Genomes Project 0.00100
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
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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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DNAH11 | - | - |
GRCh38 GRCh37 |
5283 | 5659 |
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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Uncertain significance (1) |
criteria provided, single submitter
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Feb 23, 2017 | RCV000218296.10 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jan 30, 2024 | RCV000226017.14 | |
Uncertain significance (5) |
criteria provided, multiple submitters, no conflicts
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Jun 1, 2016 | RCV000723974.25 | |
Uncertain significance (1) |
criteria provided, single submitter
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- | RCV000735289.5 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Feb 24, 2022 | RCV001160743.9 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 9, 2024 | RCV003917675.1 |
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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Uncertain significance
(Jul 18, 2014)
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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: SCV000231916.5
First in ClinVar: Jun 29, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Feb 23, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000271685.2
First in ClinVar: May 29, 2016 Last updated: Apr 09, 2018 |
Comment:
proposed classification - variant undergoing re-assessment, contact laboratory
Number of individuals with the variant: 2
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Uncertain significance
(Jul 05, 2018)
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criteria provided, single submitter
Method: clinical testing
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Primary ciliary dyskinesia
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002704127.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.R3491H variant (also known as c.10472G>A), located in coding exon 64 of the DNAH11 gene, results from a G to A substitution at nucleotide … (more)
The p.R3491H variant (also known as c.10472G>A), located in coding exon 64 of the DNAH11 gene, results from a G to A substitution at nucleotide position 10472. The arginine at codon 3491 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Feb 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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Primary ciliary dyskinesia 7
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002801340.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Benign
(Jan 30, 2024)
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criteria provided, single submitter
Method: clinical testing
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Primary ciliary dyskinesia
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000286970.9
First in ClinVar: Jul 01, 2016 Last updated: Feb 28, 2024 |
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Uncertain significance
(Jan 09, 2024)
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criteria provided, single submitter
Method: clinical testing
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DNAH11-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004727937.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The DNAH11 c.10472G>A variant is predicted to result in the amino acid substitution p.Arg3491His. This variant has been reported in the homozygous state in an … (more)
The DNAH11 c.10472G>A variant is predicted to result in the amino acid substitution p.Arg3491His. This variant has been reported in the homozygous state in an individual with skeletal anomalies and cognitive impairment who also carries a homozygous truncating variant in TMCO1 (Ji et al. 2019. PubMed ID: 30755392). This variant is reported in 0.17% of alleles in individuals of South Asian 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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Uncertain significance
(Jun 01, 2016)
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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: SCV001155048.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Uncertain significance
(-)
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criteria provided, single submitter
Method: clinical testing
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Asymmetry of the thorax
Bifid ribs Cleft palate Cleft upper lip Cognitive impairment Median cleft upper lip Periventricular leukomalacia
Affected status: yes
Allele origin:
germline
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Center for Personalized Medicine, Children's Hospital Los Angeles
Accession: SCV000854442.1
First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018 |
Sex: female
Ethnicity/Population group: Non-Hispanic, Asian/Pacific
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Uncertain significance
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Primary ciliary dyskinesia 7
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001322566.1
First in ClinVar: May 31, 2020 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Uncertain significance
(Jan 29, 2021)
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criteria provided, single submitter
Method: clinical testing
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Primary ciliary dyskinesia 7
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
paternal
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Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV003843232.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
This variant was observed in compound heterozygosity with variant c.1848+1G>T
Method: Exome sequencing
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Uncertain significance
(-)
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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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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: SCV001967880.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Uncertain significance
(-)
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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: SCV001799037.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Likely pathogenic
(Aug 29, 2023)
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Flagged submission
flagged submission
Method: clinical testing
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001791033.2
First in ClinVar: Aug 21, 2021 Last updated: Sep 07, 2023 |
Comment:
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: 30755392, … (more)
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: 30755392, 35586607, 37035737) (less)
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Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more |
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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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DNAH11 | - | - | - | - |
Text-mined citations for rs370932895 ...
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.