Genetic Variant DACT1:p.Lys633Asn (chr14-58646633-G-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_001079520.2(DACT1):c.1899G>C(p.Lys633Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,816 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DACT1
NM_001079520.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.427

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33541185).

BP6

Variant 14-58646633-G-C is Benign according to our data. Variant chr14-58646633-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 221948.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACT1	NM_001079520.2 link	c.1899G>C	p.Lys633Asn	missense_variant	Exon 4 of 4	ENST00000395153.8	NP_001072988.1	Q9NYF0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DACT1	ENST00000395153.8 link	c.1899G>C	p.Lys633Asn	missense_variant	Exon 4 of 4	5	NM_001079520.2	ENSP00000378582.3		Q9NYF0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000414

AC:

AN:

241388

AF XY:

0.00000759

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

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:

0.00000137

AC:

AN:

1458816

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725580

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.0000224

AC:

AN:

44546

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26058

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.00

AC:

AN:

85950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111022

Other (OTH)

AF:

0.00

AC:

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Rieger anomaly

Benign:1

Jan 01, 2013

Paul Sabatier University EA-4555, Paul Sabatier University

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

T;.;T;T

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.87

.;D;D;D

M_CAP

Pathogenic

0.52

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.0

.;.;M;.

PhyloP100

0.43

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-2.4

N;N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Uncertain

0.035

D;T;T;D

Polyphen

0.98

.;.;D;.

Vest4

0.46

MutPred

0.25

.;.;Loss of methylation at K670 (P = 0.006);.;

MVP

0.56

MPC

0.72

ClinPred

0.57

GERP RS

2.2

Varity_R

0.42

gMVP

0.36

Mutation Taster

=82/18

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over