14-58646014-C-T

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.1280C>T(p.Ala427Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,906 control chromosomes in the GnomAD database, including 75,377 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 (★★).

Frequency

Genomes: 𝑓 0.28 ( 6256 hom., cov: 34)

Exomes 𝑓: 0.30 ( 69121 hom. )

Consequence

DACT1
NM_001079520.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0790

Publications

29 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 Gene-Disease associations (from GenCC):

Townes-Brocks syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Townes-Brocks syndrome 2
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

DACT1 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=0.003786713).

BP6

Variant 14-58646014-C-T is Benign according to our data. Variant chr14-58646014-C-T is described in ClinVar as Benign. ClinVar VariationId is 1255448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACT1	NM_001079520.2 link	c.1280C>T	p.Ala427Val	missense_variant	Exon 4 of 4	ENST00000395153.8	NP_001072988.1	Q9NYF0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DACT1	ENST00000395153.8 link	c.1280C>T	p.Ala427Val	missense_variant	Exon 4 of 4	5	NM_001079520.2	ENSP00000378582.3		Q9NYF0-2

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42669

AN:

152086

Hom.:

6258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.300

GnomAD2 exomes

AF:

0.279

AC:

69781

AN:

250366

AF XY:

0.289

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.249

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.304

AC:

444368

AN:

1461702

Hom.:

69121

Cov.:

AF XY:

0.307

AC XY:

222987

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.260

AC:

8718

AN:

33478

American (AMR)

AF:

0.152

AC:

6789

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

7145

AN:

26136

East Asian (EAS)

AF:

0.232

AC:

9198

AN:

39700

South Asian (SAS)

AF:

0.357

AC:

30775

AN:

86256

European-Finnish (FIN)

AF:

0.232

AC:

12358

AN:

53264

Middle Eastern (MID)

AF:

0.333

AC:

1921

AN:

5768

European-Non Finnish (NFE)

AF:

0.314

AC:

348944

AN:

1111990

Other (OTH)

AF:

0.307

AC:

18520

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

21022

42043

63065

84086

105108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11394

22788

34182

45576

56970

<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:

0.280

AC:

42674

AN:

152204

Hom.:

6256

Cov.:

AF XY:

0.275

AC XY:

20477

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.262

AC:

10898

AN:

41558

American (AMR)

AF:

0.220

AC:

3359

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

922

AN:

3472

East Asian (EAS)

AF:

0.247

AC:

1277

AN:

5166

South Asian (SAS)

AF:

0.341

AC:

1641

AN:

4812

European-Finnish (FIN)

AF:

0.228

AC:

2415

AN:

10604

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.310

AC:

21062

AN:

67974

Other (OTH)

AF:

0.296

AC:

625

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1578

3157

4735

6314

7892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.302

Hom.:

31311

Bravo

AF:

0.276

TwinsUK

AF:

0.317

AC:

1175

ALSPAC

AF:

0.320

AC:

1232

ESP6500AA

AF:

0.261

AC:

1148

ESP6500EA

AF:

0.319

AC:

2747

ExAC

AF:

0.285

AC:

34577

Asia WGS

AF:

0.267

AC:

928

AN:

3478

EpiCase

AF:

0.317

EpiControl

AF:

0.321

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Townes-Brocks syndrome 2

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.6

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.027

T;.;T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.66

.;T;T;T

MetaRNN

Benign

0.0038

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.5

.;.;M;.

PhyloP100

0.079

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.057

Sift

Benign

0.045

D;D;D;D

Sift4G

Benign

0.12

T;D;D;T

Polyphen

0.033

.;.;B;.

Vest4

0.032

MPC

0.19

ClinPred

0.013

GERP RS

2.4

Varity_R

0.059

gMVP

0.16

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over