Variant 19-45785751-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004943.2(DMWD):c.1745C>T(p.Ala582Val) variant causes a missense change. The variant allele was found at a frequency of 0.0219 in 1,610,422 control chromosomes in the GnomAD database, including 442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.017 ( 36 hom., cov: 34)

Exomes 𝑓: 0.022 ( 406 hom. )

Consequence

DMWD
NM_004943.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.35

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009031743).

BP6

Variant 19-45785751-G-A is Benign according to our data. Variant chr19-45785751-G-A is described in ClinVar as [Benign]. Clinvar id is 3055409.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0167 (2539/152314) while in subpopulation NFE AF= 0.0274 (1865/68006). AF 95% confidence interval is 0.0264. There are 36 homozygotes in gnomad4. There are 1178 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 36 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMWD	NM_004943.2 linkuse as main transcript	c.1745C>T	p.Ala582Val	missense_variant	3/5	ENST00000270223.7	NP_004934.1	Q09019Q8WUW6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMWD	ENST00000270223.7 linkuse as main transcript	c.1745C>T	p.Ala582Val	missense_variant	3/5	1	NM_004943.2	ENSP00000270223.5		Q09019
ENSG00000268434	ENST00000596586.5 linkuse as main transcript	c.-38C>T		upstream_gene_variant		2		ENSP00000468837.1		M0QX08

Frequencies

GnomAD3 genomes

AF:

0.0167

AC:

2540

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00463

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.0200

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0274

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0168

AC:

4077

AN:

242626

Hom.:

AF XY:

0.0174

AC XY:

2307

AN XY:

132700

show subpopulations

Gnomad AFR exome

AF:

0.00312

Gnomad AMR exome

AF:

0.00714

Gnomad ASJ exome

AF:

0.00499

Gnomad EAS exome

AF:

0.000280

Gnomad SAS exome

AF:

0.00970

Gnomad FIN exome

AF:

0.0206

Gnomad NFE exome

AF:

0.0268

Gnomad OTH exome

AF:

0.0168

GnomAD4 exome

AF:

0.0224

AC:

32655

AN:

1458108

Hom.:

406

Cov.:

AF XY:

0.0223

AC XY:

16169

AN XY:

725044

show subpopulations

Gnomad4 AFR exome

AF:

0.00308

Gnomad4 AMR exome

AF:

0.00778

Gnomad4 ASJ exome

AF:

0.00465

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0100

Gnomad4 FIN exome

AF:

0.0214

Gnomad4 NFE exome

AF:

0.0261

Gnomad4 OTH exome

AF:

0.0178

GnomAD4 genome

AF:

0.0167

AC:

2539

AN:

152314

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1178

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00462

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00828

Gnomad4 FIN

AF:

0.0200

Gnomad4 NFE

AF:

0.0274

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.0232

Hom.:

Bravo

AF:

0.0148

TwinsUK

AF:

0.0167

AC:

ALSPAC

AF:

0.0221

AC:

ESP6500AA

AF:

0.00478

AC:

ESP6500EA

AF:

0.0263

AC:

226

ExAC

AF:

0.0173

AC:

2093

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0230

EpiControl

AF:

0.0216

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DMWD-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

T;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D

MetaRNN

Benign

0.0090

T;T

MetaSVM

Uncertain

-0.10

MutationAssessor

Benign

1.1

.;L

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.9

N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.011

D;D

Sift4G

Benign

0.067

T;T

Polyphen

0.98

D;D

Vest4

0.13

MPC

1.6

ClinPred

0.025

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over