chr2-219420151-G-C
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_001927.4(DES):c.635G>C(p.Arg212Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R212Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001927.4 missense
Scores
Clinical Significance
Conservation
Publications
- dilated cardiomyopathyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- dilated cardiomyopathy 1IInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- myofibrillar myopathy 1Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- atrioventricular blockInheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp
- arrhythmogenic right ventricular cardiomyopathyInheritance: AD Classification: MODERATE Submitted by: ClinGen
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- neurogenic scapuloperoneal syndrome, Kaeser typeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_pathogenic. The variant received 7 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DES | ENST00000373960.4 | c.635G>C | p.Arg212Pro | missense_variant | Exon 2 of 9 | 1 | NM_001927.4 | ENSP00000363071.3 | ||
DES | ENST00000477226.6 | n.109G>C | non_coding_transcript_exon_variant | Exon 1 of 8 | 4 | |||||
DES | ENST00000492726.1 | n.30G>C | non_coding_transcript_exon_variant | Exon 1 of 6 | 4 | |||||
DES | ENST00000683013.1 | n.-73G>C | upstream_gene_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461890Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 727246 show subpopulations
GnomAD4 genome Cov.: 32
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at