ClinVar Genomic variation as it relates to human health
NM_004006.3(DMD):c.8734A>G (p.Asn2912Asp)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004006.3(DMD):c.8734A>G (p.Asn2912Asp)
Variation ID: 11268 Accession: VCV000011268.43
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xp21.2 X: 31478309 (GRCh38) [ NCBI UCSC ] X: 31496426 (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 Oct 2, 2016 Sep 29, 2024 Feb 1, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004006.3:c.8734A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003997.2:p.Asn2912Asp missense NM_000109.4:c.8710A>G NP_000100.3:p.Asn2904Asp missense NM_004009.3:c.8722A>G NP_004000.1:p.Asn2908Asp missense NM_004010.3:c.8365A>G NP_004001.1:p.Asn2789Asp missense NM_004011.4:c.4711A>G NP_004002.3:p.Asn1571Asp missense NM_004012.4:c.4702A>G NP_004003.2:p.Asn1568Asp missense NM_004013.3:c.1354A>G NP_004004.2:p.Asn452Asp missense NM_004014.3:c.547A>G NP_004005.2:p.Asn183Asp missense NM_004020.4:c.1354A>G NP_004011.3:p.Asn452Asp missense NM_004021.3:c.1354A>G NP_004012.2:p.Asn452Asp missense NM_004022.3:c.1354A>G NP_004013.2:p.Asn452Asp missense NM_004023.3:c.1354A>G NP_004014.2:p.Asn452Asp missense NC_000023.11:g.31478309T>C NC_000023.10:g.31496426T>C NG_012232.1:g.1866301A>G LRG_199:g.1866301A>G LRG_199t1:c.8734A>G LRG_199p1:p.Asn2912Asp - Protein change
- N2912D, N1571D, N2789D, N452D, N183D, N2908D, N1568D, N2904D
- Other names
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p.N2912D:AAT>GAT
- Canonical SPDI
- NC_000023.11:31478308:T:C
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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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0.03709 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD), exomes 0.02126
Exome Aggregation Consortium (ExAC) 0.02224
The Genome Aggregation Database (gnomAD) 0.02976
Trans-Omics for Precision Medicine (TOPMed) 0.03266
1000 Genomes Project 0.03709
1000 Genomes Project 30x 0.03725
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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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| DMD | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
9344 | 9638 | |
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. |
|---|---|---|---|---|
| Benign (4) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000012019.38 | |
| Benign (8) |
criteria provided, multiple submitters, no conflicts
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Mar 7, 2019 | RCV000080811.34 | |
| Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000264708.13 | |
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Dystrophin deficiency
|
Benign (1) |
no assertion criteria provided
|
Aug 2, 2019 | RCV001831563.9 |
| Benign (1) |
criteria provided, single submitter
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Oct 23, 2015 | RCV000242355.11 | |
| Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Nov 29, 2023 | RCV000711470.22 |
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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|---|---|---|---|---|---|
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Benign
(-)
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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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PreventionGenetics, part of Exact Sciences
Accession: SCV000309948.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Aug 08, 2014)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000112713.8
First in ClinVar: Jan 22, 2014 Last updated: Oct 02, 2016 |
Number of individuals with the variant: 21
Sex: mixed
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Benign
(Mar 21, 2015)
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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: SCV000268975.2
First in ClinVar: May 29, 2016 Last updated: Oct 02, 2016 |
Comment:
p.Asn2912Asp in exon 59 of DMD: This variant is not expected to have clinical si gnificance because it has been identified in 7.6% (802/10506) of … (more)
p.Asn2912Asp in exon 59 of DMD: This variant is not expected to have clinical si gnificance because it has been identified in 7.6% (802/10506) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org/; dbSNP rs1800278). (less)
Number of individuals with the variant: 11
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Benign
(Mar 07, 2019)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001360766.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: DMD c.8734A>G (p.Asn2912Asp) results in a conservative amino acid change located in in a spectrin/alpha-actinin repeat (IPR018159) of the encoded protein sequence. Five … (more)
Variant summary: DMD c.8734A>G (p.Asn2912Asp) results in a conservative amino acid change located in in a spectrin/alpha-actinin repeat (IPR018159) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.022 in 200085 control chromosomes in the gnomAD database, including 59 homozygotes and 1416 hemizygotes. The observed variant frequency is significantly higher than expected for a pathogenic variant in DMD causing Dystrophinopathies phenotype, strongly suggesting that the variant is benign. Seven ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign (6x) and once as likely benign. Based on the evidence outlined above, the variant was classified as benign. (less)
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Benign
(May 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Duchenne muscular dystrophy
Affected status: no
Allele origin:
germline
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Pars Genome Lab
Accession: SCV001736777.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
Sex: mixed
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Duchenne muscular dystrophy
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000560840.7
First in ClinVar: Oct 11, 2015 Last updated: Feb 14, 2024 |
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Benign
(Nov 29, 2023)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603355.8
First in ClinVar: Oct 02, 2016 Last updated: Feb 20, 2024 |
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Likely benign
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(X-linked inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005209170.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
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Benign
(Aug 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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Duchenne muscular dystrophy
Affected status: unknown
Allele origin:
germline
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Phosphorus, Inc.
Accession: SCV000679896.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Number of individuals with the variant: 2
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Benign
(Jan 17, 2014)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000168146.11
First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Sep 11, 2017)
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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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Athena Diagnostics
Accession: SCV000841838.1
First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018 |
|
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 3B
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000482224.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Benign
(Oct 23, 2015)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000318156.7
First in ClinVar: Oct 02, 2016 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as 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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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
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: SCV001798109.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Benign
(Aug 02, 2019)
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no assertion criteria provided
Method: clinical testing
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Becker muscular dystrophy
Cardiomyopathy Duchenne muscular dystrophy Dystrophin deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002080247.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
|
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Uncertain significance
(Sep 01, 1994)
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no assertion criteria provided
Method: literature only
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RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000032253.4
First in ClinVar: Apr 04, 2013 Last updated: Mar 18, 2023 |
Comment on evidence:
This variant, formerly titled DUCHENNE MUSCULAR DYSTROPHY, has been reclassified based on a review of the gnomAD database by Hamosh (2018). In a patient with … (more)
This variant, formerly titled DUCHENNE MUSCULAR DYSTROPHY, has been reclassified based on a review of the gnomAD database by Hamosh (2018). In a patient with Duchenne muscular dystrophy (DMD; 310200), Lenk et al. (1994) identified an A-to-G substitution at nucleotide 8942 in exon 59, substituting an aspartic acid for asparagine-2912. Hamosh (2018) found that the N2912D variant was present in 4,370 of 200,085 alleles and in 59 homozygotes and 1,416 hemizygotes in the gnomAD database (April 19, 2018). (less)
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001740119.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not specified
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: SCV001928939.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 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
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| DMD Mutations in 576 Dystrophinopathy Families: A Step Forward in Genotype-Phenotype Correlations. | Juan-Mateu J | PloS one | 2015 | PMID: 26284620 |
| Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
| Disease variants in genomes of 44 centenarians. | Freudenberg-Hua Y | Molecular genetics & genomic medicine | 2014 | PMID: 25333069 |
| A systematic approach to assessing the clinical significance of genetic variants. | Duzkale H | Clinical genetics | 2013 | PMID: 24033266 |
| XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing. | Piton A | American journal of human genetics | 2013 | PMID: 23871722 |
| Free the data: one laboratory's approach to knowledge-based genomic variant classification and preparation for EMR integration of genomic data. | Bean LJ | Human mutation | 2013 | PMID: 23757202 |
| Genetic diagnosis of Duchenne and Becker muscular dystrophy using next-generation sequencing technology: comprehensive mutational search in a single platform. | Lim BC | Journal of medical genetics | 2011 | PMID: 21969337 |
| A population-based study of dystrophin mutations in Canada. | Mah JK | The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques | 2011 | PMID: 21515508 |
| Missense mutations in dystrophin that trigger muscular dystrophy decrease protein stability and lead to cross-beta aggregates. | Singh SM | Proceedings of the National Academy of Sciences of the United States of America | 2010 | PMID: 20696926 |
| Mutational spectrum of DMD mutations in dystrophinopathy patients: application of modern diagnostic techniques to a large cohort. | Flanigan KM | Human mutation | 2009 | PMID: 19937601 |
| A Two-amino Acid Mutation Encountered in Duchenne Muscular Dystrophy Decreases Stability of the Rod Domain 23 (R23) Spectrin-like Repeat of Dystrophin. | Legardinier S | The Journal of biological chemistry | 2009 | PMID: 19158079 |
| Small mutations of the DMD gene in Taiwanese families. | Hwa HL | Journal of the Formosan Medical Association = Taiwan yi zhi | 2008 | PMID: 18583217 |
| DGGE-based whole-gene mutation scanning of the dystrophin gene in Duchenne and Becker muscular dystrophy patients. | Hofstra RM | Human mutation | 2004 | PMID: 14695533 |
| Mutations in the dystrophin gene are associated with sporadic dilated cardiomyopathy. | Feng J | Molecular genetics and metabolism | 2002 | PMID: 12359139 |
| Rapid DNA haplotyping using a multiplex heteroduplex approach: application to Duchenne muscular dystrophy carrier testing. | Prior TW | Human mutation | 1995 | PMID: 7599638 |
| Carrier detection in DMD families with point mutations, using PCR-SSCP and direct sequencing. | Lenk U | Neuromuscular disorders : NMD | 1994 | PMID: 7881286 |
| Hamosh, A. Personal Communication. 2018. Baltimore, Md. | - | - | - | - |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DMD | - | - | - | - |
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Text-mined citations for rs1800278 ...
HelpRecord last updated Nov 03, 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.