rs369537705
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_001927.4(DES):c.1011C>T(p.Ala337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
DES
NM_001927.4 synonymous
NM_001927.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.423
Genes affected
DES (HGNC:2770): (desmin) This gene encodes a muscle-specific class III intermediate filament. Homopolymers of this protein form a stable intracytoplasmic filamentous network connecting myofibrils to each other and to the plasma membrane. Mutations in this gene are associated with desmin-related myopathy, a familial cardiac and skeletal myopathy (CSM), and with distal myopathies. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
Variant 2-219420941-C-T is Benign according to our data. Variant chr2-219420941-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 541305.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.423 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DES | NM_001927.4 | c.1011C>T | p.Ala337= | synonymous_variant | 5/9 | ENST00000373960.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DES | ENST00000373960.4 | c.1011C>T | p.Ala337= | synonymous_variant | 5/9 | 1 | NM_001927.4 | P1 | |
DES | ENST00000477226.6 | n.485C>T | non_coding_transcript_exon_variant | 4/8 | 4 | ||||
DES | ENST00000492726.1 | n.406C>T | non_coding_transcript_exon_variant | 4/6 | 4 | ||||
DES | ENST00000683013.1 | n.399C>T | non_coding_transcript_exon_variant | 3/7 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000719 AC: 18AN: 250422Hom.: 0 AF XY: 0.0000960 AC XY: 13AN XY: 135392
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GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461412Hom.: 0 Cov.: 38 AF XY: 0.0000413 AC XY: 30AN XY: 726982
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152292Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74466
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Desmin-related myofibrillar myopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at