Genetic Variant DACT2:p.Ala595Ala (chr6-168307972-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_214462.5(DACT2):c.1785G>A(p.Ala595Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00364 in 1,551,042 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 16 hom. )

Consequence

DACT2
NM_214462.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.30

Variant links:

Genes affected

DACT2 (HGNC:21231): (dishevelled binding antagonist of beta catenin 2) Predicted to enable several functions, including beta-catenin binding activity; delta-catenin binding activity; and protein kinase C binding activity. Predicted to be involved in several processes, including epithelial cell morphogenesis; inner medullary collecting duct development; and negative regulation of nodal signaling pathway. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DACT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 6-168307972-C-T is Benign according to our data. Variant chr6-168307972-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657141.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-8.3 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACT2	NM_214462.5 link	c.1785G>A	p.Ala595Ala	synonymous_variant	Exon 4 of 4	ENST00000366795.4	NP_999627.2	Q5SW24-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DACT2	ENST00000366795.4 link	c.1785G>A	p.Ala595Ala	synonymous_variant	Exon 4 of 4	2	NM_214462.5	ENSP00000355760.3	Q5SW24-1
DACT2	ENST00000610183.1 link	c.1275G>A	p.Ala425Ala	synonymous_variant	Exon 3 of 3	1		ENSP00000476573.1	Q5SW24-2
DACT2	ENST00000607983.1 link	c.561G>A	p.Ala187Ala	synonymous_variant	Exon 2 of 2	1		ENSP00000476434.1	Q5SW24-3
DACT2	ENST00000366796.7 link	c.658+2196G>A		intron_variant	Intron 3 of 5	1		ENSP00000355761.2	Q5SW24-4

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

390

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00368

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00256

AC:

391

AN:

152698

Hom.:

AF XY:

0.00260

AC XY:

211

AN XY:

81170

show subpopulations

Gnomad AFR exome

AF:

0.000769

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00686

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00132

Gnomad FIN exome

AF:

0.000331

Gnomad NFE exome

AF:

0.00337

Gnomad OTH exome

AF:

0.00858

GnomAD4 exome

AF:

0.00376

AC:

5253

AN:

1398738

Hom.:

Cov.:

AF XY:

0.00385

AC XY:

2657

AN XY:

689938

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00238

Gnomad4 ASJ exome

AF:

0.00656

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.00162

Gnomad4 FIN exome

AF:

0.000287

Gnomad4 NFE exome

AF:

0.00421

Gnomad4 OTH exome

AF:

0.00367

GnomAD4 genome

AF:

0.00256

AC:

390

AN:

152304

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

173

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00368

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00376

Hom.:

Bravo

AF:

0.00266

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DACT2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.068

DANN

Benign

0.61

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