chr14-58646682-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001079520.2(DACT1):c.1948T>C(p.Tyr650His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000955 in 1,612,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

DACT1
NM_001079520.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.60

Publications

0 publications found

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:

LINC01500 (HGNC:51166): (long intergenic non-protein coding RNA 1500)

LINC01500 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023557872).

BP6

Variant 14-58646682-T-C is Benign according to our data. Variant chr14-58646682-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 743594.

BS2

High AC in GnomAd4 at 89 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079520.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DACT1	NM_001079520.2	MANE Select	c.1948T>C	p.Tyr650His	missense	Exon 4 of 4	NP_001072988.1	Q9NYF0-2
DACT1	NM_016651.6		c.2059T>C	p.Tyr687His	missense	Exon 4 of 4	NP_057735.2
DACT1	NR_046093.2		n.1728T>C		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DACT1	ENST00000395153.8	TSL:5 MANE Select	c.1948T>C	p.Tyr650His	missense	Exon 4 of 4	ENSP00000378582.3	Q9NYF0-2
DACT1	ENST00000335867.4	TSL:1	c.2059T>C	p.Tyr687His	missense	Exon 4 of 4	ENSP00000337439.4	Q9NYF0-1
DACT1	ENST00000707126.1		c.1948T>C	p.Tyr650His	missense	Exon 4 of 4	ENSP00000516754.1	Q9NYF0-2

Frequencies

GnomAD3 genomes

AF:

0.000592

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000896

AC:

AN:

245428

AF XY:

0.0000448

show subpopulations

Gnomad AFR exome

AF:

0.00146

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000445

AC:

AN:

1460574

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

726630

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

33476

American (AMR)

AF:

0.0000224

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111848

Other (OTH)

AF:

0.0000331

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000585

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.00212

AC:

AN:

41544

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000201

Hom.:

Bravo

AF:

0.000559

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

DACT1-related disorder (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.039

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.3

PhyloP100

1.6

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.0

REVEL

Benign

0.087

Sift

Benign

0.031

Sift4G

Benign

0.29

Polyphen

0.99

Vest4

0.43

MVP

0.26

MPC

0.77

ClinPred

0.059

GERP RS

3.2

Varity_R

0.057

gMVP

0.33

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over