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NM_004006.3(DMD):c.2539A>G (p.Thr847Ala)

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(1);Likely benign(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Sep 23, 2021)
Last evaluated:
Oct 30, 2020
Accession:
VCV000195493.7
Variation ID:
195493
Description:
single nucleotide variant
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NM_004006.3(DMD):c.2539A>G (p.Thr847Ala)

Allele ID
192654
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
Xp21.1
Genomic location
X: 32491360 (GRCh38) GRCh38 UCSC
X: 32509477 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_004006.2:c.2539A>G NP_003997.1:p.Thr847Ala missense
NC_000023.10:g.32509477T>C
NC_000023.11:g.32491360T>C
... more HGVS
Protein change
T847A, T839A, T843A, T724A
Other names
-
Canonical SPDI
NC_000023.11:32491359:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
0.00026 (C)

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00007
Exome Aggregation Consortium (ExAC) 0.00006
The Genome Aggregation Database (gnomAD) 0.00018
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00028
The Genome Aggregation Database (gnomAD) 0.00034
1000 Genomes Project 0.00026
Trans-Omics for Precision Medicine (TOPMed) 0.00044
Trans-Omics for Precision Medicine (TOPMed) 0.00040
Links
ClinGen: CA241939
dbSNP: rs138145424
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Apr 28, 2015 RCV000223116.5
Uncertain significance 1 criteria provided, single submitter Oct 30, 2020 RCV000685504.4
Likely benign 1 criteria provided, single submitter Mar 24, 2020 RCV000620846.2
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Jun 26, 2020 RCV000724731.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
DMD Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
5376 5598

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Apr 28, 2015)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000271655.2
Submitted: (Mar 21, 2019)
Evidence details
Comment:
The p.Thr847Ala variant in DMD has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 4/8508 African chromosomes, inclu ding … (more)
Uncertain significance
(Jun 13, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000227672.5
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Benign
(Jun 26, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000619814.2
Submitted: (Sep 23, 2021)
Evidence details
Likely benign
(Mar 24, 2020)
criteria provided, single submitter
Method: clinical testing
Cardiovascular phenotype
Allele origin: germline
Ambry Genetics
Accession: SCV000737010.3
Submitted: (Nov 30, 2020)
Evidence details
Comment:
In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Uncertain significance
(Oct 30, 2020)
criteria provided, single submitter
Method: clinical testing
Duchenne muscular dystrophy
Allele origin: germline
Invitae
Accession: SCV000812987.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces threonine with alanine at codon 847 of the DMD protein (p.Thr847Ala). The threonine residue is moderately conserved and there is a … (more)

Functional evidence

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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 this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DMD - - - -

Text-mined citations for rs138145424...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021