19-45770204-C-CCAGCAG

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_004409.5(DMPK):c.*283_*284insCTGCTG 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 0.010 (20 hom., cov: 0)
  • Exomes 𝑓: 0.013 (409 hom.)
• Consequence: DMPK NM_004409.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 Benign. Variant got -12 ACMG points.

• BP6: Variant 19-45770204-C-CCAGCAG is Benign according to our data. Variant chr19-45770204-C-CCAGCAG is described in ClinVar as [Benign]. Clinvar id is 810803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 20 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMPK	NM_004409.5	c.*283_*284insCTGCTG		3_prime_UTR_variant	15/15	ENST00000291270.9
DM1-AS	NR_147193.1	n.337-1229_337-1224dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMPK	ENST00000291270.9	c.*283_*284insCTGCTG		3_prime_UTR_variant	15/15	5	NM_004409.5	A2
DM1-AS	ENST00000590076.2	n.337-1229_337-1224dup		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1563 AN: 149884 Hom.: 20 Cov.: 0

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.0621

Gnomad AMR AF: 0.00956

Gnomad ASJ AF: 0.0119

Gnomad EAS AF: 0.00498

Gnomad SAS AF: 0.00686

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.00975

GnomAD4 exome AF: 0.0126 AC: 7130 AN: 564860 Hom.: 409 Cov.: 0 AF XY: 0.0125 AC XY: 3755 AN XY: 300518

Gnomad4 AFR exome AF: 0.00279

Gnomad4 AMR exome AF: 0.00791

Gnomad4 ASJ exome AF: 0.0112

Gnomad4 EAS exome AF: 0.00676

Gnomad4 SAS exome AF: 0.00685

Gnomad4 FIN exome AF: 0.0131

Gnomad4 NFE exome AF: 0.0149

Gnomad4 OTH exome AF: 0.0134

GnomAD4 genome AF: 0.0104 AC: 1565 AN: 150000 Hom.: 20 Cov.: 0 AF XY: 0.00979 AC XY: 716 AN XY: 73140

Gnomad4 AFR AF: 0.00325

Gnomad4 AMR AF: 0.00955

Gnomad4 ASJ AF: 0.0119

Gnomad4 EAS AF: 0.00499

Gnomad4 SAS AF: 0.00666

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0146

Gnomad4 OTH AF: 0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

DMPK: BS1, BS2 -

Steinert myotonic dystrophy syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Neuromuscular Research, Maastricht University Medical Centre

Nov 26, 2019

- -

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;