chr14-58646712-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001079520.2(DACT1):c.1978G>A(p.Gly660Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,612,976 control chromosomes in the GnomAD database, including 35,862 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G660A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.25 ( 5527 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30335 hom. )

Consequence

DACT1
NM_001079520.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.94

Publications

25 publications found

Variant links:

Genes affected

DACT1 (HGNC:17748): (dishevelled binding antagonist of beta catenin 1) The protein encoded by this gene belongs to the dapper family, characterized by the presence of PDZ-binding motif at the C-terminus. It interacts with, and positively regulates dishevelled-mediated signaling pathways during development. Depletion of this mRNA from xenopus embryos resulted in loss of notochord and head structures, and mice lacking this gene died shortly after birth from severe posterior malformations. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

DACT1 links:

LINC01500 (HGNC:51166): (long intergenic non-protein coding RNA 1500)

LINC01500 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032674968).

BP6

Variant 14-58646712-G-A is Benign according to our data. Variant chr14-58646712-G-A is described in ClinVar as Benign. ClinVar VariationId is 1257885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079520.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DACT1	NM_001079520.2	MANE Select	c.1978G>A	p.Gly660Ser	missense	Exon 4 of 4	NP_001072988.1
DACT1	NM_016651.6		c.2089G>A	p.Gly697Ser	missense	Exon 4 of 4	NP_057735.2
DACT1	NR_046093.2		n.1758G>A		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DACT1	ENST00000395153.8	TSL:5 MANE Select	c.1978G>A	p.Gly660Ser	missense	Exon 4 of 4	ENSP00000378582.3
DACT1	ENST00000335867.4	TSL:1	c.2089G>A	p.Gly697Ser	missense	Exon 4 of 4	ENSP00000337439.4
DACT1	ENST00000707126.1		c.1978G>A	p.Gly660Ser	missense	Exon 4 of 4	ENSP00000516754.1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38374

AN:

151982

Hom.:

5512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.259

GnomAD2 exomes

AF:

0.230

AC:

56667

AN:

246124

AF XY:

0.222

show subpopulations

Gnomad AFR exome

AF:

0.386

Gnomad AMR exome

AF:

0.362

Gnomad ASJ exome

AF:

0.256

Gnomad EAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.197

Gnomad OTH exome

AF:

0.234

GnomAD4 exome

AF:

0.197

AC:

287951

AN:

1460876

Hom.:

30335

Cov.:

AF XY:

0.197

AC XY:

143174

AN XY:

726790

show subpopulations

African (AFR)

AF:

0.387

AC:

12964

AN:

33474

American (AMR)

AF:

0.357

AC:

15936

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

6873

AN:

26112

East Asian (EAS)

AF:

0.133

AC:

5273

AN:

39696

South Asian (SAS)

AF:

0.209

AC:

18007

AN:

86236

European-Finnish (FIN)

AF:

0.181

AC:

9535

AN:

52700

Middle Eastern (MID)

AF:

0.278

AC:

1595

AN:

5746

European-Non Finnish (NFE)

AF:

0.184

AC:

204869

AN:

1111878

Other (OTH)

AF:

0.214

AC:

12899

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

14651

29301

43952

58602

73253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7320

14640

21960

29280

36600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.253

AC:

38427

AN:

152100

Hom.:

5527

Cov.:

AF XY:

0.250

AC XY:

18613

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.379

AC:

15713

AN:

41472

American (AMR)

AF:

0.301

AC:

4600

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

886

AN:

3468

East Asian (EAS)

AF:

0.140

AC:

724

AN:

5160

South Asian (SAS)

AF:

0.200

AC:

966

AN:

4820

European-Finnish (FIN)

AF:

0.168

AC:

1783

AN:

10602

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.191

AC:

13005

AN:

67964

Other (OTH)

AF:

0.257

AC:

542

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1439

2878

4318

5757

7196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.211

Hom.:

4213

Bravo

AF:

0.269

TwinsUK

AF:

0.180

AC:

667

ALSPAC

AF:

0.177

AC:

684

ESP6500AA

AF:

0.358

AC:

1574

ESP6500EA

AF:

0.191

AC:

1642

ExAC

AF:

0.227

AC:

27491

Asia WGS

AF:

0.195

AC:

676

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

DACT1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.8

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.015

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

PhyloP100

1.9

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.74

REVEL

Benign

0.040

Sift

Benign

0.37

Sift4G

Benign

0.16

Polyphen

0.0020

Vest4

0.049

MPC

0.18

ClinPred

0.0034

GERP RS

0.84

Varity_R

0.034

gMVP

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over