19-45785448-A-T

Position:

• chr19-45785448-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887

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]

ENSG00000268434 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DMWD	NM_004943.2	c.1902+146T>A		intron_variant		ENST00000270223.7	NP_004934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMWD	ENST00000270223.7	c.1902+146T>A		intron_variant		1	NM_004943.2	ENSP00000270223.5
ENSG00000268434	ENST00000596586.5	c.120+146T>A		intron_variant		2		ENSP00000468837.1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131292 AN: 152006 Hom.: 56987 Cov.: 31

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

GnomAD3 exomes AF: 0.857 AC: 28518 AN: 33294 Hom.: 12245 AF XY: 0.854 AC XY: 14524 AN XY: 17016

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 SAS exome AF: 0.876

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.: 61 AF XY: 0.833 AC XY: 494295 AN XY: 593702

Gnomad4 AFR exome AF: 0.952

Gnomad4 AMR exome AF: 0.886

Gnomad4 ASJ exome AF: 0.804

Gnomad4 EAS exome AF: 0.883

Gnomad4 SAS exome AF: 0.881

Gnomad4 FIN exome AF: 0.782

Gnomad4 NFE exome AF: 0.825

Gnomad4 OTH exome AF: 0.843

GnomAD4 genome AF: 0.864 AC: 131407 AN: 152124 Hom.: 57040 Cov.: 31 AF XY: 0.862 AC XY: 64127 AN XY: 74372

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.805

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.845

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
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs3760843; hg19: chr19-46288706;