Variant chr19-45785819-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004943.2(DMWD):c.1677T>C(p.Ser559Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 1,611,122 control chromosomes in the GnomAD database, including 361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.027 ( 189 hom., cov: 34)

Exomes 𝑓: 0.0029 ( 172 hom. )

Consequence

DMWD
NM_004943.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.76

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 19-45785819-A-G is Benign according to our data. Variant chr19-45785819-A-G is described in ClinVar as [Benign]. Clinvar id is 3056601.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMWD	NM_004943.2 linkuse as main transcript	c.1677T>C	p.Ser559Ser	synonymous_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.1677T>C	p.Ser559Ser	synonymous_variant	3/5	1	NM_004943.2	ENSP00000270223.5	Q09019
DMWD	ENST00000377735.7 linkuse as main transcript	c.1677T>C	p.Ser559Ser	synonymous_variant	3/4	5		ENSP00000366964.3	G5E9A7
DMWD	ENST00000602829.1 linkuse as main transcript	c.90T>C	p.Ser30Ser	synonymous_variant	1/1	6		ENSP00000473377.1	R4GMW3
ENSG00000268434	ENST00000593999.1 linkuse as main transcript	n.153T>C		non_coding_transcript_exon_variant	1/3	2		ENSP00000471312.1	M0R0L4

Frequencies

GnomAD3 genomes

AF:

0.0270

AC:

4111

AN:

152130

Hom.:

189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0937

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00962

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.00642

AC:

1521

AN:

236896

Hom.:

AF XY:

0.00498

AC XY:

651

AN XY:

130640

show subpopulations

Gnomad AFR exome

AF:

0.0943

Gnomad AMR exome

AF:

0.00453

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000257

Gnomad OTH exome

AF:

0.00238

GnomAD4 exome

AF:

0.00289

AC:

4215

AN:

1458874

Hom.:

172

Cov.:

AF XY:

0.00245

AC XY:

1776

AN XY:

725870

show subpopulations

Gnomad4 AFR exome

AF:

0.0979

Gnomad4 AMR exome

AF:

0.00524

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.00666

GnomAD4 genome

AF:

0.0270

AC:

4115

AN:

152248

Hom.:

189

Cov.:

AF XY:

0.0267

AC XY:

1985

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0935

Gnomad4 AMR

AF:

0.00960

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000530

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.00848

Hom.:

Bravo

AF:

0.0302

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000474

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 20, 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

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.51

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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