rs1060502638
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The NM_004006.3(DMD):c.2110C>T(p.Pro704Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000827 in 1,208,939 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P704P) has been classified as Likely benign.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.2110C>T | p.Pro704Ser | missense_variant | 17/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.2110C>T | p.Pro704Ser | missense_variant | 17/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000448 AC: 5AN: 111691Hom.: 0 Cov.: 23 AF XY: 0.0000590 AC XY: 2AN XY: 33889
GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183059Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67629
GnomAD4 exome AF: 0.00000456 AC: 5AN: 1097248Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1AN XY: 362774
GnomAD4 genome ? AF: 0.0000448 AC: 5AN: 111691Hom.: 0 Cov.: 23 AF XY: 0.0000590 AC XY: 2AN XY: 33889
ClinVar
Submissions by phenotype
Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 11, 2018 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 05, 2021 | The p.P704S variant (also known as c.2110C>T), located in coding exon 17 of the DMD gene, results from a C to T substitution at nucleotide position 2110. The proline at codon 704 is replaced by serine, an amino acid with similar properties. Based on data from gnomAD, the T allele has an overall frequency of 0.001% (2/204912) total alleles studied, with no hemizygotes observed. The highest observed frequency was 0.01% (2/19011) of African/African American alleles. This amino acid position is well conserved in available vertebrate species; however, serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Duchenne muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 30, 2023 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 704 of the DMD protein (p.Pro704Ser). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 409910). 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 with a negative predictive value of 95%. 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