rs58409037

chr2-219421384-TGCCAGTGAG-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM4 PP3 PP5_Moderate

The NM_001927.4(DES):c.1076_1084del(p.Glu359_Ser361del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DES NM_001927.4 inframe_deletion
• Clinical Significance: Pathogenic criteria provided, single submitter P:2 O:1
• Conservation: PhyloP100: 9.86

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM1: In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 9 uncertain in NM_001927.4
• PM4: Nonframeshift variant in NON repetitive region in NM_001927.4.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 2-219421384-TGCCAGTGAG-T is Pathogenic according to our data. Variant chr2-219421384-TGCCAGTGAG-T is described in ClinVar as [Pathogenic]. Clinvar id is 66391.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-219421384-TGCCAGTGAG-T is described in Lovd as [Pathogenic]. Variant chr2-219421384-TGCCAGTGAG-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DES	NM_001927.4	c.1076_1084del	p.Glu359_Ser361del	inframe_deletion	6/9	ENST00000373960.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DES	ENST00000373960.4	c.1076_1084del	p.Glu359_Ser361del	inframe_deletion	6/9	1	NM_001927.4	P1
DES	ENST00000477226.6	n.550_558del		non_coding_transcript_exon_variant	5/8	4
DES	ENST00000492726.1	n.471_479del		non_coding_transcript_exon_variant	5/6	4
DES	ENST00000683013.1	n.464_472del		non_coding_transcript_exon_variant	4/7

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1 Other:1

not provided, no classification provided	literature only	Epithelial Biology; Institute of Medical Biology, Singapore	-	- -
Pathogenic, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 21, 2017	- -

Desmin-related myofibrillar myopathy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 29, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58409037; hg19: chr2-220286106;