chr19-45770204-CCAG-C

Variant names:

• chr19-45770204-CCAG-C
• NM_004409.5:c.*281_*283delCTG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004409.5(DMPK):​c.*281_*283delCTG 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -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 VariationId is 810785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 500 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004409.5. 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
	DMPK	NM_004409.5	MANE Select	c.*281_*283delCTG		3_prime_UTR	Exon 15 of 15	NP_004400.4
	DMPK	NM_001424163.1		c.*274_*276delCTG		3_prime_UTR	Exon 16 of 16	NP_001411092.1
	DMPK	NM_001288764.2		c.*281_*283delCTG		3_prime_UTR	Exon 16 of 16	NP_001275693.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMPK	ENST00000291270.9	TSL:5 MANE Select	c.*281_*283delCTG		3_prime_UTR	Exon 15 of 15	ENSP00000291270.4	Q09013-9
	DMPK	ENST00000343373.10	TSL:1	c.*274_*276delCTG		3_prime_UTR	Exon 15 of 15	ENSP00000345997.4	Q09013-16
	DMPK	ENST00000447742.6	TSL:1	c.*281_*283delCTG		3_prime_UTR	Exon 15 of 15	ENSP00000413417.1	Q09013-11

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

African (AFR) AF: 0.00279 AC: 40 AN: 14340

American (AMR) AF: 0.00336 AC: 104 AN: 30958

Ashkenazi Jewish (ASJ) AF: 0.00686 AC: 120 AN: 17498

East Asian (EAS) AF: 0.00737 AC: 225 AN: 30528

South Asian (SAS) AF: 0.00702 AC: 414 AN: 58970

European-Finnish (FIN) AF: 0.00394 AC: 129 AN: 32738

Middle Eastern (MID) AF: 0.00369 AC: 9 AN: 2436

European-Non Finnish (NFE) AF: 0.00621 AC: 2158 AN: 347356

Other (OTH) AF: 0.00582 AC: 173 AN: 29708

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

African (AFR) AF: 0.00157 AC: 64 AN: 40874

American (AMR) AF: 0.00186 AC: 28 AN: 15084

Ashkenazi Jewish (ASJ) AF: 0.00377 AC: 13 AN: 3446

East Asian (EAS) AF: 0.00279 AC: 14 AN: 5010

South Asian (SAS) AF: 0.00623 AC: 29 AN: 4658

European-Finnish (FIN) AF: 0.00438 AC: 45 AN: 10284

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00438 AC: 295 AN: 67406

Other (OTH) AF: 0.00482 AC: 10 AN: 2074

Alfa AF: 0.00 Hom.: 128

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Steinert myotonic dystrophy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr19-46273462;