ClinVar Genomic variation as it relates to human health
NM_001386795.1(DTNA):c.1480G>A (p.Asp494Asn)
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(3); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001386795.1(DTNA):c.1480G>A (p.Asp494Asn)
Variation ID: 46412 Accession: VCV000046412.17
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 18q12.1 18: 34851876 (GRCh38) [ NCBI UCSC ] 18: 32431840 (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 Jun 8, 2015 Mar 16, 2024 Dec 13, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001386795.1:c.1480G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001373724.1:p.Asp494Asn missense NM_001198938.2:c.1219G>A NP_001185867.1:p.Asp407Asn missense NM_001198939.2:c.1219G>A NP_001185868.1:p.Asp407Asn missense NM_001198940.2:c.1219G>A NP_001185869.1:p.Asp407Asn missense NM_001198941.2:c.1219G>A NP_001185870.1:p.Asp407Asn missense NM_001198942.1:c.526G>A NP_001185871.1:p.Asp176Asn missense NM_001198943.1:c.469G>A NP_001185872.1:p.Asp157Asn missense NM_001198944.1:c.355G>A NP_001185873.1:p.Asp119Asn missense NM_001198945.2:c.649G>A NP_001185874.1:p.Asp217Asn missense NM_001386753.1:c.1219G>A NP_001373682.1:p.Asp407Asn missense NM_001386754.1:c.1309G>A NP_001373683.1:p.Asp437Asn missense NM_001386755.1:c.1309G>A NP_001373684.1:p.Asp437Asn missense NM_001386756.1:c.1309G>A NP_001373685.1:p.Asp437Asn missense NM_001386757.1:c.1309G>A NP_001373686.1:p.Asp437Asn missense NM_001386758.1:c.1309G>A NP_001373687.1:p.Asp437Asn missense NM_001386759.1:c.1309G>A NP_001373688.1:p.Asp437Asn missense NM_001386760.1:c.1306G>A NP_001373689.1:p.Asp436Asn missense NM_001386761.1:c.1228G>A NP_001373690.1:p.Asp410Asn missense NM_001386762.1:c.1225G>A NP_001373691.1:p.Asp409Asn missense NM_001386763.1:c.1219G>A NP_001373692.1:p.Asp407Asn missense NM_001386764.1:c.1219G>A NP_001373693.1:p.Asp407Asn missense NM_001386765.1:c.1219G>A NP_001373694.1:p.Asp407Asn missense NM_001386766.1:c.1219G>A NP_001373695.1:p.Asp407Asn missense NM_001386767.1:c.1219G>A NP_001373696.1:p.Asp407Asn missense NM_001386768.1:c.1216G>A NP_001373697.1:p.Asp406Asn missense NM_001386769.1:c.1216G>A NP_001373698.1:p.Asp406Asn missense NM_001386770.1:c.1309G>A NP_001373699.1:p.Asp437Asn missense NM_001386771.1:c.1219G>A NP_001373700.1:p.Asp407Asn missense NM_001386772.1:c.1219G>A NP_001373701.1:p.Asp407Asn missense NM_001386773.1:c.1216G>A NP_001373702.1:p.Asp406Asn missense NM_001386774.1:c.1216G>A NP_001373703.1:p.Asp406Asn missense NM_001386788.1:c.1480G>A NP_001373717.1:p.Asp494Asn missense NM_001390.5:c.1399G>A NP_001381.2:p.Asp467Asn missense NM_001391.5:c.1399G>A NP_001382.2:p.Asp467Asn missense NM_032975.4:c.1228G>A NP_116757.2:p.Asp410Asn missense NM_032978.7:c.1390G>A NP_116760.2:p.Asp464Asn missense NM_032979.5:c.1228G>A NP_116761.2:p.Asp410Asn missense NM_032980.4:c.343G>A NP_116762.2:p.Asp115Asn missense NM_032981.5:c.265G>A NP_116763.1:p.Asp89Asn missense NC_000018.10:g.34851876G>A NC_000018.9:g.32431840G>A NG_009201.1:g.363587G>A LRG_756:g.363587G>A LRG_756t1:c.1399G>A LRG_756p1:p.Asp467Asn LRG_756t2:c.1228G>A LRG_756p2:p.Asp410Asn LRG_756t3:c.1390G>A LRG_756p3:p.Asp464Asn LRG_756t4:c.1480G>A LRG_756p4:p.Asp494Asn - Protein change
- D410N, D467N, D464N, D115N, D119N, D217N, D89N, D157N, D176N, D407N, D406N, D409N, D436N, D437N, D494N
- Other names
- p.D464N:GAT>AAT
- Canonical SPDI
- NC_000018.10:34851875: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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0.00020 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00007
The Genome Aggregation Database (gnomAD), exomes 0.00008
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023
The Genome Aggregation Database (gnomAD) 0.00037
Trans-Omics for Precision Medicine (TOPMed) 0.00037
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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DTNA | - | - |
GRCh38 GRCh37 |
608 | 650 |
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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Apr 27, 2012 | RCV000039668.15 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Nov 23, 2021 | RCV000171933.12 | |
Likely benign (1) |
criteria provided, single submitter
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Dec 13, 2023 | RCV000547018.17 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 20, 2023 | RCV003934944.1 |
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
(Nov 23, 2021)
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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: SCV000235899.12
First in ClinVar: Jul 05, 2015 Last updated: Mar 04, 2023 |
Comment:
Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious … (more)
Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar (ClinVar Variant ID#46412; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 26582918) (less)
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Likely benign
(Jan 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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DTNA-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004761462.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Uncertain significance
(Jun 24, 2013)
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criteria provided, single submitter
Method: research
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Not provided
Affected status: unknown
Allele origin:
unknown
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Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000050935.1 First in ClinVar: Jun 08, 2015 Last updated: Jun 08, 2015
Comments (2):
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less)
Medical sequencing
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Number of individuals with the variant: 1
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Uncertain significance
(Apr 27, 2012)
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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: SCV000063357.5
First in ClinVar: May 03, 2013 Last updated: May 29, 2016 |
Comment:
Variant classified as Uncertain Significance - Favor Benign. The Asp410Asn varia nt (DTNA) has not been reported in the literature nor previously identified by o … (more)
Variant classified as Uncertain Significance - Favor Benign. The Asp410Asn varia nt (DTNA) has not been reported in the literature nor previously identified by o ur laboratory. Computational analyses (biochemical amino acid properties, conser vation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or aga inst an impact to the protein. This variant has been identified in 0.08% (3/3738 ) of African American chromosomes from a broad population by the NHLBI Exome Se quencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs144880521). While t his frequency suggests that this variant is more likely benign, it is too low to confidently rule out a disease causing role. Additional information is needed t o fully assess its clinical significance. (less)
Number of individuals with the variant: 1
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Likely benign
(Dec 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Left ventricular noncompaction 1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000642421.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
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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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs144880521 ...
HelpRecord last updated May 01, 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.