2-219418432-T-TGCGCCCGCCAGCC

Variant names:

• chr2-219418432-T-TGCGCCCGCCAGCC
• rs794728983
• NM_001927.4:c.-30_-18dupGCGCCCGCCAGCC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001927.4(DES):​c.-30_-18dupGCGCCCGCCAGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 1,552,212 control chromosomes in the GnomAD database, including 173 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (101 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (72 hom.)
• Consequence: DES NM_001927.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.502
• Publications: 0 publications found

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• myofibrillar myopathy

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• myofibrillar myopathy 1

  Inheritance: SD, AD, AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• atrioventricular block

  Inheritance: AR, AD 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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 2-219418432-T-TGCGCCCGCCAGCC is Benign according to our data. Variant chr2-219418432-T-TGCGCCCGCCAGCC is described in ClinVar as Benign. ClinVar VariationId is 201699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0611 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001927.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DES	NM_001927.4	MANE Select	c.-30_-18dupGCGCCCGCCAGCC		5_prime_UTR	Exon 1 of 9	NP_001918.3
	DES	NM_001382708.1		c.-30_-18dupGCGCCCGCCAGCC		5_prime_UTR	Exon 1 of 9	NP_001369637.1
	DES	NM_001382712.1		c.-30_-18dupGCGCCCGCCAGCC		5_prime_UTR	Exon 1 of 9	NP_001369641.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DES	ENST00000373960.4	TSL:1 MANE Select	c.-30_-18dupGCGCCCGCCAGCC		5_prime_UTR	Exon 1 of 9	ENSP00000363071.3	P17661
	DES	ENST00000942906.1		c.-30_-18dupGCGCCCGCCAGCC		5_prime_UTR	Exon 1 of 10	ENSP00000612965.1
	DES	ENST00000942898.1		c.-30_-18dupGCGCCCGCCAGCC		5_prime_UTR	Exon 1 of 9	ENSP00000612957.1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2771 AN: 152006 Hom.: 99 Cov.: 32

Gnomad AFR AF: 0.0631

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00779

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00110 AC: 181 AN: 165222 AF XY: 0.000796

Gnomad AFR exome AF: 0.0239

Gnomad AMR exome AF: 0.000906

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000272

Gnomad OTH exome AF: 0.00187

GnomAD4 exome AF: 0.00160 AC: 2237 AN: 1400096 Hom.: 72 Cov.: 29 AF XY: 0.00134 AC XY: 930 AN XY: 694576

African (AFR) AF: 0.0607 AC: 1791 AN: 29530

American (AMR) AF: 0.00234 AC: 91 AN: 38950

Ashkenazi Jewish (ASJ) AF: 0.0000404 AC: 1 AN: 24752

East Asian (EAS) AF: 0.00 AC: 0 AN: 35420

South Asian (SAS) AF: 0.000149 AC: 12 AN: 80740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37266

Middle Eastern (MID) AF: 0.000730 AC: 3 AN: 4108

European-Non Finnish (NFE) AF: 0.0000825 AC: 90 AN: 1091254

Other (OTH) AF: 0.00429 AC: 249 AN: 58076

GnomAD4 genome AF: 0.0183 AC: 2779 AN: 152116 Hom.: 101 Cov.: 32 AF XY: 0.0176 AC XY: 1309 AN XY: 74382

African (AFR) AF: 0.0631 AC: 2618 AN: 41496

American (AMR) AF: 0.00778 AC: 119 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67964

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.00993 Hom.: 3

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.50
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs794728983; hg19: chr2-220283154;