Genetic Variant DACT2:p.Gly707Gly (chr6-168307636-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_214462.5(DACT2):c.2121C>T(p.Gly707Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,547,220 control chromosomes in the GnomAD database, including 255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 24 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 231 hom. )

Consequence

DACT2
NM_214462.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0140

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-168307636-G-A is Benign according to our data. Variant chr6-168307636-G-A is described in ClinVar as [Benign]. Clinvar id is 769702.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.014 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACT2	NM_214462.5 link	c.2121C>T	p.Gly707Gly	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.2121C>T	p.Gly707Gly	synonymous_variant	Exon 4 of 4	2	NM_214462.5	ENSP00000355760.3	Q5SW24-1
DACT2	ENST00000610183.1 link	c.1611C>T	p.Gly537Gly	synonymous_variant	Exon 3 of 3	1		ENSP00000476573.1	Q5SW24-2
DACT2	ENST00000607983.1 link	c.897C>T	p.Gly299Gly	synonymous_variant	Exon 2 of 2	1		ENSP00000476434.1	Q5SW24-3
DACT2	ENST00000366796.7 link	c.658+2532C>T		intron_variant	Intron 3 of 5	1		ENSP00000355761.2	Q5SW24-4

Frequencies

GnomAD3 genomes

AF:

0.00628

AC:

956

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0775

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.0126

AC:

1908

AN:

151982

Hom.:

AF XY:

0.0111

AC XY:

898

AN XY:

80582

show subpopulations

Gnomad AFR exome

AF:

0.00140

Gnomad AMR exome

AF:

0.0267

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0765

Gnomad SAS exome

AF:

0.00305

Gnomad FIN exome

AF:

0.0163

Gnomad NFE exome

AF:

0.000825

Gnomad OTH exome

AF:

0.00958

GnomAD4 exome

AF:

0.00469

AC:

6536

AN:

1394966

Hom.:

231

Cov.:

AF XY:

0.00455

AC XY:

3124

AN XY:

687340

show subpopulations

Gnomad4 AFR exome

AF:

0.000603

Gnomad4 AMR exome

AF:

0.0258

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.00349

Gnomad4 FIN exome

AF:

0.0162

Gnomad4 NFE exome

AF:

0.000612

Gnomad4 OTH exome

AF:

0.00514

GnomAD4 genome

AF:

0.00629

AC:

958

AN:

152254

Hom.:

Cov.:

AF XY:

0.00707

AC XY:

526

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.0169

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0785

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.00118

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00211

Hom.:

Bravo

AF:

0.00707

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 14, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.71

DANN

Benign

0.58

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