Variant 19-45785915-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_004943.2(DMWD):c.1581A>G(p.Thr527Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000619 in 1,603,064 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0029 ( 4 hom., cov: 34)

Exomes 𝑓: 0.00038 ( 4 hom. )

Consequence

DMWD
NM_004943.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.48

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 19-45785915-T-C is Benign according to our data. Variant chr19-45785915-T-C is described in ClinVar as [Benign]. Clinvar id is 3042541.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.48 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMWD	NM_004943.2 linkuse as main transcript	c.1581A>G	p.Thr527Thr	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.1581A>G	p.Thr527Thr	synonymous_variant	3/5	1	NM_004943.2	ENSP00000270223.5	Q09019
DMWD	ENST00000377735.7 linkuse as main transcript	c.1581A>G	p.Thr527Thr	synonymous_variant	3/4	5		ENSP00000366964.3	G5E9A7
ENSG00000268434	ENST00000593999.1 linkuse as main transcript	n.57A>G		non_coding_transcript_exon_variant	1/3	2		ENSP00000471312.1	M0R0L4
DMWD	ENST00000602829.1 linkuse as main transcript	c.-7A>G		upstream_gene_variant		6		ENSP00000473377.1	R4GMW3

Frequencies

GnomAD3 genomes

AF:

0.00291

AC:

443

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.000831

AC:

189

AN:

227536

Hom.:

AF XY:

0.000634

AC XY:

AN XY:

126110

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.000560

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000586

Gnomad NFE exome

AF:

0.000138

Gnomad OTH exome

AF:

0.000348

GnomAD4 exome

AF:

0.000381

AC:

553

AN:

1450798

Hom.:

Cov.:

AF XY:

0.000335

AC XY:

242

AN XY:

722140

show subpopulations

Gnomad4 AFR exome

AF:

0.0113

Gnomad4 AMR exome

AF:

0.000582

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000343

Gnomad4 NFE exome

AF:

0.0000612

Gnomad4 OTH exome

AF:

0.000896

GnomAD4 genome

AF:

0.00289

AC:

440

AN:

152266

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00996

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000904

Hom.:

Bravo

AF:

0.00346

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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 27, 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

-0.89

CADD

Benign

0.29

DANN

Benign

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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