rs12920

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001927.4(DES):​c.1014G>A​(p.Leu338Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L338L) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DES
NM_001927.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.307
Variant links:
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 -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP7
Synonymous conserved (PhyloP=0.307 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DESNM_001927.4 linkc.1014G>A p.Leu338Leu synonymous_variant Exon 5 of 9 ENST00000373960.4 NP_001918.3 P17661Q53SB5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DESENST00000373960.4 linkc.1014G>A p.Leu338Leu synonymous_variant Exon 5 of 9 1 NM_001927.4 ENSP00000363071.3 P17661
DESENST00000477226.6 linkn.488G>A non_coding_transcript_exon_variant Exon 4 of 8 4
DESENST00000492726.1 linkn.409G>A non_coding_transcript_exon_variant Exon 4 of 6 4
DESENST00000683013.1 linkn.402G>A non_coding_transcript_exon_variant Exon 3 of 7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460800
Hom.:
0
Cov.:
49
AF XY:
0.00
AC XY:
0
AN XY:
726634
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
CADD
Benign
12
DANN
Benign
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-220285666; API