chr19-45770204-CCAG-C

Position:

• chr19-45770204-CCAG-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.*281_*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 0.00542 in 714,546 control chromosomes in the GnomAD database, including 157 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0060 (157 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-CCAG-C is Benign according to our data. Variant chr19-45770204-CCAG-C is described in ClinVar as [Benign]. Clinvar id is 810785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 157 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMPK	NM_004409.5	c.*281_*283del		3_prime_UTR_variant	15/15	ENST00000291270.9	NP_004400.4
DM1-AS	NR_147193.1	n.337-1226_337-1224del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMPK	ENST00000291270.9	c.*281_*283del		3_prime_UTR_variant	15/15	5	NM_004409.5	ENSP00000291270	A2
DM1-AS	ENST00000590076.2	n.337-1226_337-1224del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00333 AC: 499 AN: 149898 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00186

Gnomad ASJ AF: 0.00377

Gnomad EAS AF: 0.00279

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.00438

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00439

Gnomad OTH AF: 0.00439

GnomAD4 exome AF: 0.00597 AC: 3372 AN: 564532 Hom.: 157 AF XY: 0.00627 AC XY: 1882 AN XY: 300286

Gnomad4 AFR exome AF: 0.00279

Gnomad4 AMR exome AF: 0.00336

Gnomad4 ASJ exome AF: 0.00686

Gnomad4 EAS exome AF: 0.00737

Gnomad4 SAS exome AF: 0.00702

Gnomad4 FIN exome AF: 0.00394

Gnomad4 NFE exome AF: 0.00621

Gnomad4 OTH exome AF: 0.00582

GnomAD4 genome AF: 0.00333 AC: 500 AN: 150014 Hom.: 0 Cov.: 0 AF XY: 0.00328 AC XY: 240 AN XY: 73150

Gnomad4 AFR AF: 0.00157

Gnomad4 AMR AF: 0.00186

Gnomad4 ASJ AF: 0.00377

Gnomad4 EAS AF: 0.00279

Gnomad4 SAS AF: 0.00623

Gnomad4 FIN AF: 0.00438

Gnomad4 NFE AF: 0.00438

Gnomad4 OTH AF: 0.00482

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

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;