chr19-45785623-T-C

Position:

• chr19-45785623-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004943.2(DMWD):​c.1873A>G​(p.Ile625Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: DMWD NM_004943.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21862096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMWD	NM_004943.2	c.1873A>G	p.Ile625Val	missense_variant	3/5	ENST00000270223.7	NP_004934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMWD	ENST00000270223.7	c.1873A>G	p.Ile625Val	missense_variant	3/5	1	NM_004943.2	ENSP00000270223.5
ENSG00000268434	ENST00000596586.5	c.91A>G	p.Ile31Val	missense_variant	1/5	2		ENSP00000468837.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.1873A>G (p.I625V) alteration is located in exon 3 (coding exon 3) of the DMWD gene. This alteration results from a A to G substitution at nucleotide position 1873, causing the isoleucine (I) at amino acid position 625 to be replaced by a valine (V). 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	.;.;T;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D;D;D;D;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.57	.;.;.;N;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.13	.;.;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.64	.;.;T;T;T
Sift4G	Benign	0.61	.;T;T;T;T
Polyphen		0.24, 0.091	.;.;B;B;.
Vest4		0.34, 0.31
MutPred		0.50		.;.;Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);.;
MVP		0.28
MPC		0.79
ClinPred		0.47	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-46288881;