rs370941715

Variant names:

• chr6-168307635-C-T
• rs370941715
• NM_214462.5:c.2122G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-168307635-C-T
• chr6-168307635-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_214462.5(DACT2):​c.2122G>A​(p.Ala708Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000414 in 1,547,144 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: DACT2 NM_214462.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.674
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024136662).

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.2122G>A	p.Ala708Thr	missense	Exon 4 of 4	NP_999627.2	Q5SW24-1
	DACT2	NM_001286350.2		c.1612G>A	p.Ala538Thr	missense	Exon 3 of 3	NP_001273279.1	Q5SW24-2
	DACT2	NM_001286351.2		c.658+2533G>A		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.2122G>A	p.Ala708Thr	missense	Exon 4 of 4	ENSP00000355760.3	Q5SW24-1
	DACT2	ENST00000610183.1	TSL:1	c.1612G>A	p.Ala538Thr	missense	Exon 3 of 3	ENSP00000476573.1	Q5SW24-2
	DACT2	ENST00000607983.1	TSL:1	c.898G>A	p.Ala300Thr	missense	Exon 2 of 2	ENSP00000476434.1	Q5SW24-3

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152166 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000396 AC: 6 AN: 151690 AF XY: 0.0000124

Gnomad AFR exome AF: 0.000762

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000301 AC: 42 AN: 1394860 Hom.: 0 Cov.: 36 AF XY: 0.0000276 AC XY: 19 AN XY: 687326

African (AFR) AF: 0.000793 AC: 25 AN: 31520

American (AMR) AF: 0.0000845 AC: 3 AN: 35500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24990

East Asian (EAS) AF: 0.00 AC: 0 AN: 35622

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.0000102 AC: 11 AN: 1076144

Other (OTH) AF: 0.0000346 AC: 2 AN: 57782

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152284 Hom.: 1 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74460

African (AFR) AF: 0.000481 AC: 20 AN: 41566

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000692 Hom.: 0

Bravo AF: 0.000140

ESP6500AA AF: 0.00217 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000713 AC: 2

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	0.070
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.9
DANN	Benign	0.93
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.67
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.046
Sift	Benign	0.56	T
Sift4G	Benign	0.36	T
Polyphen		0.65	P
Vest4		0.033
MVP		0.030
ClinPred		0.014	T
GERP RS		-0.65
Varity_R		0.025
gMVP		0.050
Mutation Taster		=94/6	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: rs370941715; hg19: chr6-168708315;