Variant 14-58646658-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4BP6_ModerateBS2_Supporting

The NM_001079520.2(DACT1):c.1924T>C(p.Trp642Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000532 in 1,610,318 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 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00053 ( 2 hom. )

Consequence

DACT1
NM_001079520.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.64

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30948746).

BP6

Variant 14-58646658-T-C is Benign according to our data. Variant chr14-58646658-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 734469.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 77 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACT1	NM_001079520.2 linkuse as main transcript	c.1924T>C	p.Trp642Arg	missense_variant	4/4	ENST00000395153.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACT1	ENST00000395153.8 linkuse as main transcript	c.1924T>C	p.Trp642Arg	missense_variant	4/4	5	NM_001079520.2		Q9NYF0-2
LINC01500	ENST00000648996.1 linkuse as main transcript	n.28T>C		non_coding_transcript_exon_variant	1/14

Frequencies

GnomAD3 genomes

AF:

0.000507

AC:

AN:

151778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000560

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000587

AC:

141

AN:

240294

Hom.:

AF XY:

0.000622

AC XY:

AN XY:

131912

show subpopulations

Gnomad AFR exome

AF:

0.0000696

Gnomad AMR exome

AF:

0.000321

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000590

Gnomad FIN exome

AF:

0.00168

Gnomad NFE exome

AF:

0.000683

Gnomad OTH exome

AF:

0.000510

GnomAD4 exome

AF:

0.000535

AC:

780

AN:

1458540

Hom.:

Cov.:

AF XY:

0.000520

AC XY:

377

AN XY:

725534

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.000537

Gnomad4 OTH exome

AF:

0.000283

GnomAD4 genome

AF:

0.000507

AC:

AN:

151778

Hom.:

Cov.:

AF XY:

0.000621

AC XY:

AN XY:

74102

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000946

Gnomad4 NFE

AF:

0.000560

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000482

Hom.:

Bravo

AF:

0.000552

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000471

AC:

ExAC

AF:

0.000588

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000536

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;.;T;T

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.71

.;T;T;T

M_CAP

Pathogenic

0.59

MetaRNN

Benign

0.31

T;T;T;T

MetaSVM

Uncertain

-0.094

MutationAssessor

Pathogenic

3.3

.;.;M;.

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-8.7

D;D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.042

D;D;T;D

Polyphen

1.0

.;.;D;.

Vest4

0.74

MutPred

0.39

.;.;Loss of ubiquitination at K680 (P = 0.0247);.;

MVP

0.53

MPC

0.97

ClinPred

0.15

GERP RS

5.5

Varity_R

0.64

gMVP

0.27

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