2-219421470-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_001927.4(DES):c.1154T>C(p.Leu385Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 14/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L385V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001927.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DES | NM_001927.4 | c.1154T>C | p.Leu385Pro | missense_variant | 6/9 | ENST00000373960.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DES | ENST00000373960.4 | c.1154T>C | p.Leu385Pro | missense_variant | 6/9 | 1 | NM_001927.4 | P1 | |
DES | ENST00000477226.6 | n.628T>C | non_coding_transcript_exon_variant | 5/8 | 4 | ||||
DES | ENST00000492726.1 | n.549T>C | non_coding_transcript_exon_variant | 5/6 | 4 | ||||
DES | ENST00000683013.1 | n.542T>C | non_coding_transcript_exon_variant | 4/7 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Desmin-related myofibrillar myopathy Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 10, 2000 | - - |
not provided Other:1
not provided, no classification provided | literature only | Epithelial Biology; Institute of Medical Biology, Singapore | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at