Variant 14-58638470-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001079520.2(DACT1):c.268C>T(p.Leu90Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,356,664 control chromosomes in the GnomAD database, including 191,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24432 hom., cov: 34)

Exomes 𝑓: 0.53 ( 167502 hom. )

Consequence

DACT1
NM_001079520.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.504

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 14-58638470-C-T is Benign according to our data. Variant chr14-58638470-C-T is described in ClinVar as [Benign]. Clinvar id is 1255447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-58638470-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.504 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 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.268C>T	p.Leu90Leu	synonymous_variant	1/4	ENST00000395153.8	NP_001072988.1	Q9NYF0-2
DACT1	NM_016651.6 linkuse as main transcript	c.268C>T	p.Leu90Leu	synonymous_variant	1/4		NP_057735.2	Q9NYF0-1
DACT1	NR_046093.2 linkuse as main transcript	n.126-2266C>T		intron_variant
DACT1	NR_165650.1 linkuse as main transcript	n.126-2266C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DACT1	ENST00000395153.8 linkuse as main transcript	c.268C>T	p.Leu90Leu	synonymous_variant	1/4	5	NM_001079520.2	ENSP00000378582.3		Q9NYF0-2

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

85085

AN:

151986

Hom.:

24399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.668

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.547

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.669

Gnomad NFE

AF:

0.529

Gnomad OTH

AF:

0.576

GnomAD3 exomes

AF:

0.530

AC:

53940

AN:

101724

Hom.:

14359

AF XY:

0.533

AC XY:

30075

AN XY:

56408

show subpopulations

Gnomad AFR exome

AF:

0.673

Gnomad AMR exome

AF:

0.532

Gnomad ASJ exome

AF:

0.517

Gnomad EAS exome

AF:

0.366

Gnomad SAS exome

AF:

0.575

Gnomad FIN exome

AF:

0.461

Gnomad NFE exome

AF:

0.543

Gnomad OTH exome

AF:

0.536

GnomAD4 exome

AF:

0.525

AC:

632462

AN:

1204564

Hom.:

167502

Cov.:

AF XY:

0.527

AC XY:

307269

AN XY:

583266

show subpopulations

Gnomad4 AFR exome

AF:

0.677

Gnomad4 AMR exome

AF:

0.541

Gnomad4 ASJ exome

AF:

0.525

Gnomad4 EAS exome

AF:

0.361

Gnomad4 SAS exome

AF:

0.578

Gnomad4 FIN exome

AF:

0.463

Gnomad4 NFE exome

AF:

0.525

Gnomad4 OTH exome

AF:

0.544

GnomAD4 genome

AF:

0.560

AC:

85170

AN:

152100

Hom.:

24432

Cov.:

AF XY:

0.554

AC XY:

41189

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.668

Gnomad4 AMR

AF:

0.548

Gnomad4 ASJ

AF:

0.513

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.559

Gnomad4 FIN

AF:

0.450

Gnomad4 NFE

AF:

0.529

Gnomad4 OTH

AF:

0.570

Alfa

AF:

0.483

Hom.:

2889

Bravo

AF:

0.571

Asia WGS

AF:

0.473

AC:

1642

AN:

3476

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

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.2

DANN

Benign

0.96

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