14-58640877-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001079520.2(DACT1):c.478+9T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,614,078 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (4 hom.)
• Consequence: DACT1 NM_001079520.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0630

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 14-58640877-T-G is Benign according to our data. Variant chr14-58640877-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 711385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 158 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACT1	NM_001079520.2	c.478+9T>G		intron_variant		ENST00000395153.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACT1	ENST00000395153.8	c.478+9T>G		intron_variant		5	NM_001079520.2

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 158 AN: 152166 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00198

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00102 AC: 257 AN: 251372 Hom.: 0 AF XY: 0.00102 AC XY: 139 AN XY: 135866

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00179 AC: 2615 AN: 1461794 Hom.: 4 Cov.: 31 AF XY: 0.00179 AC XY: 1302 AN XY: 727192

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000402

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.000337

Gnomad4 NFE exome AF: 0.00225

Gnomad4 OTH exome AF: 0.000960

GnomAD4 genome AF: 0.00104 AC: 158 AN: 152284 Hom.: 0 Cov.: 33 AF XY: 0.00101 AC XY: 75 AN XY: 74456

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00198

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00154 Hom.: 0

Bravo AF: 0.00118

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

DACT1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 29, 2022

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
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.6
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs150385273; hg19: chr14-59107595;