6-168307590-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_214462.5(DACT2):​c.2167G>C​(p.Gly723Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 1,549,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

DACT2
NM_214462.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.721
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.064145416).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DACT2NM_214462.5 linkc.2167G>C p.Gly723Arg missense_variant Exon 4 of 4 ENST00000366795.4 NP_999627.2 Q5SW24-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DACT2ENST00000366795.4 linkc.2167G>C p.Gly723Arg missense_variant Exon 4 of 4 2 NM_214462.5 ENSP00000355760.3 Q5SW24-1
DACT2ENST00000610183.1 linkc.1657G>C p.Gly553Arg missense_variant Exon 3 of 3 1 ENSP00000476573.1 Q5SW24-2
DACT2ENST00000607983.1 linkc.943G>C p.Gly315Arg missense_variant Exon 2 of 2 1 ENSP00000476434.1 Q5SW24-3
DACT2ENST00000366796.7 linkc.658+2578G>C intron_variant Intron 3 of 5 1 ENSP00000355761.2 Q5SW24-4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152120
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000659
AC:
1
AN:
151710
Hom.:
0
AF XY:
0.0000124
AC XY:
1
AN XY:
80548
show subpopulations
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 SAS exome
AF:
0.0000444
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000143
AC:
2
AN:
1397402
Hom.:
0
Cov.:
37
AF XY:
0.00000145
AC XY:
1
AN XY:
689104
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000253
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152120
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000389
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
0.15
DANN
Benign
0.76
DEOGEN2
Benign
0.045
T;.;.
Eigen
Benign
-0.92
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.46
T;T;T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.064
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.22
N;.;.
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-0.80
N;.;.
REVEL
Benign
0.076
Sift
Benign
0.40
T;.;.
Sift4G
Benign
0.52
T;T;T
Polyphen
0.68
P;.;.
Vest4
0.096
MutPred
0.39
Loss of sheet (P = 0.0181);.;.;
MVP
0.040
ClinPred
0.078
T
GERP RS
-0.92
Varity_R
0.047
gMVP
0.083

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs191740169; hg19: chr6-168708270; API