chr19-45770204-C-CCAGCAGCAG

Position:

• chr19-45770204-C-CCAGCAGCAG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004409.5(DMPK):​c.*283_*284insCTGCTGCTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0077 (18 hom.)
• Consequence: DMPK NM_004409.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

Genes affected

DMPK (HGNC:2933): (DM1 protein kinase) The protein encoded by this gene is a serine-threonine kinase that is closely related to other kinases that interact with members of the Rho family of small GTPases. Substrates for this enzyme include myogenin, the beta-subunit of the L-type calcium channels, and phospholemman. The 3' untranslated region of this gene contains 5-38 copies of a CTG trinucleotide repeat. Expansion of this unstable motif to 50-5,000 copies causes myotonic dystrophy type I, which increases in severity with increasing repeat element copy number. Repeat expansion is associated with condensation of local chromatin structure that disrupts the expression of genes in this region. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2016]

DM1-AS (HGNC:53125): (DM1 locus antisense RNA)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 19-45770204-C-CCAGCAGCAG is Benign according to our data. Variant chr19-45770204-C-CCAGCAGCAG is described in ClinVar as [Benign]. Clinvar id is 810810.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMPK	NM_004409.5	c.*283_*284insCTGCTGCTG		3_prime_UTR_variant	15/15	ENST00000291270.9	NP_004400.4
DM1-AS	NR_147193.1	n.337-1232_337-1224dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMPK	ENST00000291270.9	c.*283_*284insCTGCTGCTG		3_prime_UTR_variant	15/15	5	NM_004409.5	ENSP00000291270	A2
DM1-AS	ENST00000590076.2	n.337-1232_337-1224dup		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00626 AC: 938 AN: 149902 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.0158

Gnomad AMR AF: 0.00518

Gnomad ASJ AF: 0.0162

Gnomad EAS AF: 0.00438

Gnomad SAS AF: 0.00557

Gnomad FIN AF: 0.00904

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.00832

Gnomad OTH AF: 0.0107

GnomAD4 exome AF: 0.00767 AC: 4333 AN: 565026 Hom.: 18 Cov.: 0 AF XY: 0.00761 AC XY: 2287 AN XY: 300584

Gnomad4 AFR exome AF: 0.00181

Gnomad4 AMR exome AF: 0.00520

Gnomad4 ASJ exome AF: 0.0123

Gnomad4 EAS exome AF: 0.00987

Gnomad4 SAS exome AF: 0.00510

Gnomad4 FIN exome AF: 0.0105

Gnomad4 NFE exome AF: 0.00775

Gnomad4 OTH exome AF: 0.00898

GnomAD4 genome AF: 0.00625 AC: 937 AN: 150018 Hom.: 3 Cov.: 0 AF XY: 0.00577 AC XY: 422 AN XY: 73152

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00517

Gnomad4 ASJ AF: 0.0162

Gnomad4 EAS AF: 0.00439

Gnomad4 SAS AF: 0.00536

Gnomad4 FIN AF: 0.00904

Gnomad4 NFE AF: 0.00832

Gnomad4 OTH AF: 0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Steinert myotonic dystrophy syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Neuromuscular Research, Maastricht University Medical Centre

Nov 26, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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: chr19-46273462;