2-219418680-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The ENST00000373960.4(DES):c.218G>A(p.Arg73Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000101 in 1,576,524 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R73L) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000373960.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DES | NM_001927.4 | c.218G>A | p.Arg73Gln | missense_variant | 1/9 | ENST00000373960.4 | NP_001918.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DES | ENST00000373960.4 | c.218G>A | p.Arg73Gln | missense_variant | 1/9 | 1 | NM_001927.4 | ENSP00000363071 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151954Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000983 AC: 14AN: 1424570Hom.: 0 Cov.: 92 AF XY: 0.00000993 AC XY: 7AN XY: 704904
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151954Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74230
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 14, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30564623) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 12, 2018 | - - |
Desmin-related myofibrillar myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 16, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 73 of the DES protein (p.Arg73Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with DES-related conditions. ClinVar contains an entry for this variant (Variation ID: 500027). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 27, 2022 | The p.R73Q variant (also known as c.218G>A), located in coding exon 1 of the DES gene, results from a G to A substitution at nucleotide position 218. The arginine at codon 73 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at