19-45785448-A-C

Variant names:

• chr19-45785448-A-C
• rs3760843
• NM_004943.2:c.1902+146T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004943.2(DMWD):​c.1902+146T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DMWD NM_004943.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887
• Publications: 15 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004943.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMWD	NM_004943.2	MANE Select	c.1902+146T>G		intron	N/A	NP_004934.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMWD	ENST00000270223.7	TSL:1 MANE Select	c.1902+146T>G		intron	N/A	ENSP00000270223.5
	ENSG00000268434	ENST00000595946.1	TSL:2	c.120+146T>G		intron	N/A	ENSP00000469741.1
	DMWD	ENST00000537879.1	TSL:1	c.66+146T>G		intron	N/A	ENSP00000444820.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.10e-7 AC: 1 AN: 1233822 Hom.: 0 Cov.: 61 AF XY: 0.00 AC XY: 0 AN XY: 593934

African (AFR) AF: 0.00 AC: 0 AN: 26046

American (AMR) AF: 0.00 AC: 0 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17874

East Asian (EAS) AF: 0.00 AC: 0 AN: 31106

South Asian (SAS) AF: 0.0000190 AC: 1 AN: 52498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3508

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1006988

Other (OTH) AF: 0.00 AC: 0 AN: 51266

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 6307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.53
DANN	Benign	0.16
PhyloP100		-0.89
PromoterAI		-0.0024	Neutral

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

Other links and lift over

dbSNP: rs3760843; hg19: chr19-46288706;