Variant 14-58646014-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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

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:

DACT1 (HGNC:):

DACT1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1255448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-58646014-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
DACT1	NM_001079520.2 linkuse as main transcript	c.1280C>T	p.Ala427Val	missense_variant	4/4	ENST00000395153.8	NP_001072988.1	Q9NYF0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DACT1	ENST00000395153.8 linkuse as main transcript	c.1280C>T	p.Ala427Val	missense_variant	4/4	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

GnomAD3 exomes

AF:

0.279

AC:

69781

AN:

250366

Hom.:

10411

AF XY:

0.289

AC XY:

39146

AN XY:

135506

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 SAS exome

AF:

0.357

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

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.232

Gnomad4 SAS exome

AF:

0.357

Gnomad4 FIN exome

AF:

0.232

Gnomad4 NFE exome

AF:

0.314

Gnomad4 OTH exome

AF:

0.307

GnomAD4 genome

AF:

0.280

AC:

42674

AN:

152204

Hom.:

6256

Cov.:

AF XY:

0.275

AC XY:

20477

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.262

Gnomad4 AMR

AF:

0.220

Gnomad4 ASJ

AF:

0.266

Gnomad4 EAS

AF:

0.247

Gnomad4 SAS

AF:

0.341

Gnomad4 FIN

AF:

0.228

Gnomad4 NFE

AF:

0.310

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.305

Hom.:

15547

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Townes-Brocks syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

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

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;.

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over