14-58638470-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001079520.2(DACT1):c.268C>T(p.Leu90=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.504

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]

ACMG classification

Verdict is Benign. Variant got -13 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_single_submitter, 1 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	UniProt
DACT1	NM_001079520.2	c.268C>T	p.Leu90=	synonymous_variant	1/4	ENST00000395153.8
DACT1	NM_016651.6	c.268C>T	p.Leu90=	synonymous_variant	1/4
DACT1	NR_046093.2	n.126-2266C>T		intron_variant, non_coding_transcript_variant
DACT1	NR_165650.1	n.126-2266C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACT1	ENST00000395153.8	c.268C>T	p.Leu90=	synonymous_variant	1/4	5	NM_001079520.2

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85085 AN: 151986 Hom.: 24399 Cov.: 34

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

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.: 50 AF XY: 0.527 AC XY: 307269 AN XY: 583266

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.: 34 AF XY: 0.554 AC XY: 41189 AN XY: 74358

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Other links and lift over

dbSNP: rs2003021; hg19: chr14-59105188; COSMIC: COSV60020048; COSMIC: COSV60020048;