19-45770204-C-CCAGCAGCAG

Variant names:

• chr19-45770204-C-CCAGCAGCAG
• NM_004409.5:c.*275_*283dupCTGCTGCTG

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.*275_*283dupCTGCTGCTG 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
• 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-C-CCAGCAGCAG is Benign according to our data. Variant chr19-45770204-C-CCAGCAGCAG is described in ClinVar as Benign. ClinVar VariationId is 810810.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 937 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.*275_*283dupCTGCTGCTG		3_prime_UTR	Exon 15 of 15	NP_004400.4
	DMPK	NM_001424163.1		c.*268_*276dupCTGCTGCTG		3_prime_UTR	Exon 16 of 16	NP_001411092.1
	DMPK	NM_001288764.2		c.*275_*283dupCTGCTGCTG		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.*275_*283dupCTGCTGCTG		3_prime_UTR	Exon 15 of 15	ENSP00000291270.4	Q09013-9
	DMPK	ENST00000343373.10	TSL:1	c.*268_*276dupCTGCTGCTG		3_prime_UTR	Exon 15 of 15	ENSP00000345997.4	Q09013-16
	DMPK	ENST00000447742.6	TSL:1	c.*275_*283dupCTGCTGCTG		3_prime_UTR	Exon 15 of 15	ENSP00000413417.1	Q09013-11

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

African (AFR) AF: 0.00181 AC: 26 AN: 14350

American (AMR) AF: 0.00520 AC: 161 AN: 30978

Ashkenazi Jewish (ASJ) AF: 0.0123 AC: 216 AN: 17500

East Asian (EAS) AF: 0.00987 AC: 301 AN: 30498

South Asian (SAS) AF: 0.00510 AC: 301 AN: 58970

European-Finnish (FIN) AF: 0.0105 AC: 344 AN: 32716

Middle Eastern (MID) AF: 0.00819 AC: 20 AN: 2442

European-Non Finnish (NFE) AF: 0.00775 AC: 2697 AN: 347840

Other (OTH) AF: 0.00898 AC: 267 AN: 29732

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

African (AFR) AF: 0.00147 AC: 60 AN: 40878

American (AMR) AF: 0.00517 AC: 78 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.0162 AC: 56 AN: 3448

East Asian (EAS) AF: 0.00439 AC: 22 AN: 5008

South Asian (SAS) AF: 0.00536 AC: 25 AN: 4660

European-Finnish (FIN) AF: 0.00904 AC: 93 AN: 10286

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.00832 AC: 561 AN: 67400

Other (OTH) AF: 0.0106 AC: 22 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		=94/6	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr19-46273462;