rs398124041
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_004006.3(DMD):āc.7016A>Gā(p.His2339Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000473 in 1,205,056 control chromosomes in the GnomAD database, including 2 homozygotes. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H2339N) has been classified as Uncertain significance.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.7016A>G | p.His2339Arg | missense_variant | 48/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.7016A>G | p.His2339Arg | missense_variant | 48/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000179 AC: 2AN: 111425Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33595
GnomAD3 exomes AF: 0.0000169 AC: 3AN: 177535Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 62531
GnomAD4 exome AF: 0.0000503 AC: 55AN: 1093631Hom.: 2 Cov.: 31 AF XY: 0.0000557 AC XY: 20AN XY: 359307
GnomAD4 genome AF: 0.0000179 AC: 2AN: 111425Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33595
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 29, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 17, 2018 | This variant is associated with the following publications: (PMID: 29847600) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 17, 2023 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 15, 2015 | - - |
Duchenne muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 19, 2022 | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 2339 of the DMD protein (p.His2339Arg). This variant is present in population databases (rs398124041, gnomAD 0.001%). This missense change has been observed in individual(s) with clinical features of DMD-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 94755). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DMD protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at