Genetic Variant DMWD:c.1902+146T>A (chr19-45785448-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004943.2(DMWD):c.1902+146T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,385,458 control chromosomes in the GnomAD database, including 484,247 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.86 ( 57040 hom., cov: 31)

Exomes 𝑓: 0.83 ( 427207 hom. )

Consequence

DMWD
NM_004943.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.887

Publications

15 publications found

Variant links:

Genes affected

DMWD (HGNC:2936): (DM1 locus, WD repeat containing) Predicted to be located in dendrite; nucleus; and perikaryon. [provided by Alliance of Genome Resources, Apr 2022]

DMWD links:

ENSG00000268434 (HGNC:):

ENSG00000268434 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMWD	NM_004943.2 link	c.1902+146T>A		intron_variant	Intron 3 of 4	ENST00000270223.7	NP_004934.1	Q09019Q8WUW6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMWD	ENST00000270223.7 link	c.1902+146T>A		intron_variant	Intron 3 of 4	1	NM_004943.2	ENSP00000270223.5		Q09019
ENSG00000268434	ENST00000595946.1 link	c.120+146T>A		intron_variant	Intron 1 of 3	2		ENSP00000469741.1		M0QYC6

Frequencies

GnomAD3 genomes

AF:

0.864

AC:

131292

AN:

152006

Hom.:

56987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.948

Gnomad AMI

AF:

0.608

Gnomad AMR

AF:

0.880

Gnomad ASJ

AF:

0.805

Gnomad EAS

AF:

0.916

Gnomad SAS

AF:

0.885

Gnomad FIN

AF:

0.779

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.824

Gnomad OTH

AF:

0.845

GnomAD2 exomes

AF:

0.857

AC:

28518

AN:

33294

AF XY:

0.854

show subpopulations

Gnomad AFR exome

AF:

0.946

Gnomad AMR exome

AF:

0.877

Gnomad ASJ exome

AF:

0.780

Gnomad EAS exome

AF:

0.918

Gnomad FIN exome

AF:

0.769

Gnomad NFE exome

AF:

0.820

Gnomad OTH exome

AF:

0.831

GnomAD4 exome

AF:

0.832

AC:

1025726

AN:

1233334

Hom.:

427207

Cov.:

AF XY:

0.833

AC XY:

494295

AN XY:

593702

show subpopulations

African (AFR)

AF:

0.952

AC:

24798

AN:

26042

American (AMR)

AF:

0.886

AC:

13472

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.804

AC:

14365

AN:

17858

East Asian (EAS)

AF:

0.883

AC:

27466

AN:

31096

South Asian (SAS)

AF:

0.881

AC:

46197

AN:

52442

European-Finnish (FIN)

AF:

0.782

AC:

22893

AN:

29264

Middle Eastern (MID)

AF:

0.859

AC:

3011

AN:

3506

European-Non Finnish (NFE)

AF:

0.825

AC:

830315

AN:

1006680

Other (OTH)

AF:

0.843

AC:

43209

AN:

51238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

9474

18948

28423

37897

47371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20332

40664

60996

81328

101660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.864

AC:

131407

AN:

152124

Hom.:

57040

Cov.:

AF XY:

0.862

AC XY:

64127

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.948

AC:

39356

AN:

41532

American (AMR)

AF:

0.880

AC:

13462

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.805

AC:

2795

AN:

3470

East Asian (EAS)

AF:

0.916

AC:

4721

AN:

5154

South Asian (SAS)

AF:

0.885

AC:

4267

AN:

4822

European-Finnish (FIN)

AF:

0.779

AC:

8242

AN:

10574

Middle Eastern (MID)

AF:

0.864

AC:

254

AN:

294

European-Non Finnish (NFE)

AF:

0.824

AC:

55977

AN:

67972

Other (OTH)

AF:

0.845

AC:

1783

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

916

1832

2748

3664

4580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.840

Hom.:

6307

Bravo

AF:

0.874

Asia WGS

AF:

0.907

AC:

3155

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.51

(source)

DANN

Benign

0.43

PhyloP100

-0.89

PromoterAI

0.00040

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over