GeneBe

rs111828114

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001927.4(DES):​c.408C>A​(p.Leu136Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L136L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

DES
NM_001927.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.728

Publications

0 publications found
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]
DES Gene-Disease associations (from GenCC):
  • dilated cardiomyopathy
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • dilated cardiomyopathy 1I
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • myofibrillar myopathy 1
    Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • atrioventricular block
    Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp
  • arrhythmogenic right ventricular cardiomyopathy
    Inheritance: AD Classification: MODERATE Submitted by: ClinGen
  • familial isolated dilated cardiomyopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • neurogenic scapuloperoneal syndrome, Kaeser type
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
Variant 2-219418870-C-A is Benign according to our data. Variant chr2-219418870-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1530657.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.728 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DESNM_001927.4 linkc.408C>A p.Leu136Leu synonymous_variant Exon 1 of 9 ENST00000373960.4 NP_001918.3 P17661Q53SB5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DESENST00000373960.4 linkc.408C>A p.Leu136Leu synonymous_variant Exon 1 of 9 1 NM_001927.4 ENSP00000363071.3 P17661

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1421650
Hom.:
0
Cov.:
92
AF XY:
0.00
AC XY:
0
AN XY:
703490
African (AFR)
AF:
0.00
AC:
0
AN:
32672
American (AMR)
AF:
0.00
AC:
0
AN:
38166
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25496
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37552
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81196
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49734
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5696
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1092204
Other (OTH)
AF:
0.00
AC:
0
AN:
58934
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Desmin-related myofibrillar myopathy Benign:1
May 25, 2021
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.30
CADD
Benign
9.7
DANN
Benign
0.95
PhyloP100
0.73
PromoterAI
-0.032
Neutral
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs111828114; hg19: chr2-220283592; COSMIC: COSV64660446; COSMIC: COSV64660446; API