rs754651383

Variant names:

• chr17-7226307-C-A
• rs754651383
• NM_004422.3:c.1769G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7226307-C-A
• chr17-7226307-C-G
• chr17-7226307-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004422.3(DVL2):​c.1769G>T​(p.Arg590Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R590Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: DVL2 NM_004422.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 0 publications found

Genes affected

DVL2 (HGNC:3086): (dishevelled segment polarity protein 2) This gene encodes a member of the dishevelled (dsh) protein family. The vertebrate dsh proteins have approximately 40% amino acid sequence similarity with Drosophila dsh. This gene encodes a 90-kD protein that undergoes posttranslational phosphorylation to form a 95-kD cytoplasmic protein, which may play a role in the signal transduction pathway mediated by multiple Wnt proteins. The mechanisms of dishevelled function in Wnt signaling are likely to be conserved among metazoans. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3984645).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004422.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DVL2	NM_004422.3	MANE Select	c.1769G>T	p.Arg590Leu	missense	Exon 15 of 15	NP_004413.1	O14641

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DVL2	ENST00000005340.10	TSL:1 MANE Select	c.1769G>T	p.Arg590Leu	missense	Exon 15 of 15	ENSP00000005340.4	O14641
	DVL2	ENST00000951245.1		c.1835G>T	p.Arg612Leu	missense	Exon 15 of 15	ENSP00000621304.1
	DVL2	ENST00000930220.1		c.1823G>T	p.Arg608Leu	missense	Exon 15 of 15	ENSP00000600279.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410758 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 698590

African (AFR) AF: 0.00 AC: 0 AN: 31780

American (AMR) AF: 0.00 AC: 0 AN: 36486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22490

East Asian (EAS) AF: 0.00 AC: 0 AN: 39400

South Asian (SAS) AF: 0.00 AC: 0 AN: 78756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5498

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089878

Other (OTH) AF: 0.00 AC: 0 AN: 58116

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.67	D
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.9
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.091
Sift	Benign	0.099	T
Sift4G	Benign	0.25	T
Polyphen		0.42	B
Vest4		0.56
MutPred		0.30		Loss of MoRF binding (P = 0.0291)
MVP		0.62
MPC		0.58
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.26
gMVP		0.45
Mutation Taster		=68/32	polymorphism

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: rs754651383; hg19: chr17-7129626;