14-58638462-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001079520.2(DACT1):c.260G>T(p.Gly87Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000384 in 1,357,976 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

DACT1
NM_001079520.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.253

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0072631836).

BP6

Variant 14-58638462-G-T is Benign according to our data. Variant chr14-58638462-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 717000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd at 321 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DACT1	NM_001079520.2 linkuse as main transcript	c.260G>T	p.Gly87Val	missense_variant	1/4	ENST00000395153.8
DACT1	NM_016651.6 linkuse as main transcript	c.260G>T	p.Gly87Val	missense_variant	1/4
DACT1	NR_046093.2 linkuse as main transcript	n.126-2274G>T		intron_variant, non_coding_transcript_variant
DACT1	NR_165650.1 linkuse as main transcript	n.126-2274G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACT1	ENST00000395153.8 linkuse as main transcript	c.260G>T	p.Gly87Val	missense_variant	1/4	5	NM_001079520.2		Q9NYF0-2

Frequencies

GnomAD3 genomes

AF:

0.00211

AC:

321

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000561

AC:

AN:

99786

Hom.:

AF XY:

0.000396

AC XY:

AN XY:

55516

show subpopulations

Gnomad AFR exome

AF:

0.00741

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.000166

AC:

200

AN:

1205662

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

583850

show subpopulations

Gnomad4 AFR exome

AF:

0.00645

Gnomad4 AMR exome

AF:

0.000288

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000509

Gnomad4 OTH exome

AF:

0.000583

GnomAD4 genome

AF:

0.00211

AC:

321

AN:

152314

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

143

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00724

Gnomad4 AMR

AF:

0.000914

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000312

Hom.:

Bravo

AF:

0.00256

ESP6500AA

AF:

0.00391

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000640

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

DACT1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 16, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.53

T;T

MetaRNN

Benign

0.0073

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.077

Sift

Uncertain

0.020

D;D

Sift4G

Uncertain

0.044

D;D

Polyphen

1.0

.;D

Vest4

0.17

MVP

0.29

MPC

0.75

ClinPred

0.11

GERP RS

3.4

Varity_R

0.23

gMVP

0.11

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