19-45770204-CCAGCAGCAG-C

Variant summary

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

The NM_004409.5(DMPK):c.*275_*283del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.005 in 715,458 control chromosomes in the GnomAD database, including 247 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0053 (244 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-CCAGCAGCAG-C is Benign according to our data. Variant chr19-45770204-CCAGCAGCAG-C is described in ClinVar as [Benign]. Clinvar id is 810824.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMPK	NM_004409.5	c.*275_*283del		3_prime_UTR_variant	15/15	ENST00000291270.9
DM1-AS	NR_147193.1	n.337-1232_337-1224del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMPK	ENST00000291270.9	c.*275_*283del		3_prime_UTR_variant	15/15	5	NM_004409.5	A2
DM1-AS	ENST00000590076.2	n.337-1232_337-1224del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00384 AC: 575 AN: 149910 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.0530

Gnomad AMR AF: 0.00597

Gnomad ASJ AF: 0.000580

Gnomad EAS AF: 0.00697

Gnomad SAS AF: 0.00793

Gnomad FIN AF: 0.000681

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00429

Gnomad OTH AF: 0.00195

GnomAD4 exome AF: 0.00529 AC: 2993 AN: 565432 Hom.: 244 AF XY: 0.00550 AC XY: 1654 AN XY: 300758

Gnomad4 AFR exome AF: 0.00223

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.000742

Gnomad4 EAS exome AF: 0.00619

Gnomad4 SAS exome AF: 0.00932

Gnomad4 FIN exome AF: 0.00156

Gnomad4 NFE exome AF: 0.00475

Gnomad4 OTH exome AF: 0.00464

GnomAD4 genome AF: 0.00389 AC: 583 AN: 150026 Hom.: 3 Cov.: 0 AF XY: 0.00360 AC XY: 263 AN XY: 73152

Gnomad4 AFR AF: 0.00174

Gnomad4 AMR AF: 0.00590

Gnomad4 ASJ AF: 0.000580

Gnomad4 EAS AF: 0.00699

Gnomad4 SAS AF: 0.00794

Gnomad4 FIN AF: 0.000681

Gnomad4 NFE AF: 0.00429

Gnomad4 OTH AF: 0.00193

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;