Variant chr19-45785787-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004943.2(DMWD):c.1709G>A(p.Arg570His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000714 in 1,611,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

DMWD
NM_004943.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.251

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33922338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMWD	NM_004943.2 linkuse as main transcript	c.1709G>A	p.Arg570His	missense_variant	3/5	ENST00000270223.7	NP_004934.1	Q09019Q8WUW6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DMWD	ENST00000270223.7 linkuse as main transcript	c.1709G>A	p.Arg570His	missense_variant	3/5	1	NM_004943.2	ENSP00000270223.5	Q09019
DMWD	ENST00000377735.7 linkuse as main transcript	c.1709G>A	p.Arg570His	missense_variant	3/4	5		ENSP00000366964.3	G5E9A7
DMWD	ENST00000602829.1 linkuse as main transcript	c.122G>A	p.Arg41His	missense_variant	1/1	6		ENSP00000473377.1	R4GMW3
ENSG00000268434	ENST00000593999.1 linkuse as main transcript	n.185G>A		non_coding_transcript_exon_variant	1/3	2		ENSP00000471312.1	M0R0L4

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000418

AC:

AN:

239048

Hom.:

AF XY:

0.0000228

AC XY:

AN XY:

131302

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000755

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000726

AC:

106

AN:

1459210

Hom.:

Cov.:

AF XY:

0.0000634

AC XY:

AN XY:

725894

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000873

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

ExAC

AF:

0.00000831

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.1709G>A (p.R570H) alteration is located in exon 3 (coding exon 3) of the DMWD gene. This alteration results from a G to A substitution at nucleotide position 1709, causing the arginine (R) at amino acid position 570 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.088

T;T

Eigen

Benign

0.10

Eigen_PC

Benign

0.045

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.76

T;T

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.34

T;T

MetaSVM

Uncertain

0.039

MutationAssessor

Benign

1.0

.;L

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.25

Sift

Uncertain

0.013

D;D

Sift4G

Benign

0.10

T;T

Polyphen

1.0

D;D

Vest4

0.19

MVP

0.97

MPC

0.96

ClinPred

0.13

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.064

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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