NM_214462.5:c.1858C>T

Variant names:

• chr6-168307899-G-A
• rs904090536
• NM_214462.5:c.1858C>T

Variant summary

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

The NM_214462.5(DACT2):​c.1858C>T​(p.Arg620Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000563 in 1,385,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000069 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: DACT2 NM_214462.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

Genes affected

DACT2 (HGNC:21231): (dishevelled binding antagonist of beta catenin 2) Predicted to enable several functions, including beta-catenin binding activity; delta-catenin binding activity; and protein kinase C binding activity. Predicted to be involved in several processes, including epithelial cell morphogenesis; inner medullary collecting duct development; and negative regulation of nodal signaling pathway. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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 (MetaRNN=0.05673924).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_214462.5. 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
	DACT2	NM_214462.5	MANE Select	c.1858C>T	p.Arg620Cys	missense	Exon 4 of 4	NP_999627.2	Q5SW24-1
	DACT2	NM_001286350.2		c.1348C>T	p.Arg450Cys	missense	Exon 3 of 3	NP_001273279.1	Q5SW24-2
	DACT2	NM_001286351.2		c.658+2269C>T		intron	N/A	NP_001273280.1	Q5SW24-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DACT2	ENST00000366795.4	TSL:2 MANE Select	c.1858C>T	p.Arg620Cys	missense	Exon 4 of 4	ENSP00000355760.3	Q5SW24-1
	DACT2	ENST00000610183.1	TSL:1	c.1348C>T	p.Arg450Cys	missense	Exon 3 of 3	ENSP00000476573.1	Q5SW24-2
	DACT2	ENST00000607983.1	TSL:1	c.634C>T	p.Arg212Cys	missense	Exon 2 of 2	ENSP00000476434.1	Q5SW24-3

Frequencies

GnomAD3 genomes AF: 0.0000690 AC: 7 AN: 101430 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000642

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000661 AC: 9 AN: 136152 AF XY: 0.0000409

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000553 AC: 71 AN: 1283762 Hom.: 0 Cov.: 56 AF XY: 0.0000524 AC XY: 33 AN XY: 629312

African (AFR) AF: 0.000140 AC: 4 AN: 28564

American (AMR) AF: 0.00 AC: 0 AN: 29374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22922

East Asian (EAS) AF: 0.00 AC: 0 AN: 31138

South Asian (SAS) AF: 0.000170 AC: 10 AN: 58758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5036

European-Non Finnish (NFE) AF: 0.0000539 AC: 55 AN: 1019934

Other (OTH) AF: 0.0000380 AC: 2 AN: 52674

GnomAD4 genome AF: 0.0000690 AC: 7 AN: 101430 Hom.: 0 Cov.: 29 AF XY: 0.0000202 AC XY: 1 AN XY: 49598

African (AFR) AF: 0.000154 AC: 4 AN: 25916

American (AMR) AF: 0.00 AC: 0 AN: 9634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2408

East Asian (EAS) AF: 0.00 AC: 0 AN: 3546

South Asian (SAS) AF: 0.00 AC: 0 AN: 3392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 164

European-Non Finnish (NFE) AF: 0.0000642 AC: 3 AN: 46748

Other (OTH) AF: 0.00 AC: 0 AN: 1260

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.77	N
PhyloP100		1.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.033
Sift	Benign	0.081	T
Sift4G	Uncertain	0.053	T
Polyphen		0.13	B
Vest4		0.036
MutPred		0.32		Gain of catalytic residue at L621 (P = 0.0202)
MVP		0.030
ClinPred		0.059	T
GERP RS		-1.7
Varity_R		0.069
gMVP		0.19
Mutation Taster		=92/8	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: rs904090536; hg19: chr6-168708579;