Variant 6-39856354-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000274867.9(DAAM2):c.52G>A(p.Gly18Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00474 in 1,553,092 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 22 hom. )

Consequence

DAAM2
ENST00000274867.9 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.91

Variant links:

Genes affected

DAAM2 (HGNC:18143): (dishevelled associated activator of morphogenesis 2) Predicted to enable actin binding activity and small GTPase binding activity. Predicted to be involved in nervous system development and regulation of Wnt signaling pathway. Predicted to act upstream of or within determination of left/right symmetry. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

DAAM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009129673).

BP6

Variant 6-39856354-G-A is Benign according to our data. Variant chr6-39856354-G-A is described in ClinVar as [Benign]. Clinvar id is 771395.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM2	NM_001201427.2 linkuse as main transcript	c.52G>A	p.Gly18Arg	missense_variant	2/25	ENST00000274867.9	NP_001188356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAAM2	ENST00000274867.9 linkuse as main transcript	c.52G>A	p.Gly18Arg	missense_variant	2/25	1	NM_001201427.2	ENSP00000274867	P1	Q86T65-3

Frequencies

GnomAD3 genomes

AF:

0.00349

AC:

531

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00560

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00408

AC:

686

AN:

167966

Hom.:

AF XY:

0.00403

AC XY:

362

AN XY:

89780

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00388

Gnomad ASJ exome

AF:

0.00476

Gnomad EAS exome

AF:

0.0000942

Gnomad SAS exome

AF:

0.00153

Gnomad FIN exome

AF:

0.00204

Gnomad NFE exome

AF:

0.00620

Gnomad OTH exome

AF:

0.00572

GnomAD4 exome

AF:

0.00487

AC:

6826

AN:

1400778

Hom.:

Cov.:

AF XY:

0.00480

AC XY:

3321

AN XY:

692278

show subpopulations

Gnomad4 AFR exome

AF:

0.000735

Gnomad4 AMR exome

AF:

0.00414

Gnomad4 ASJ exome

AF:

0.00418

Gnomad4 EAS exome

AF:

0.0000862

Gnomad4 SAS exome

AF:

0.00148

Gnomad4 FIN exome

AF:

0.00191

Gnomad4 NFE exome

AF:

0.00564

Gnomad4 OTH exome

AF:

0.00346

GnomAD4 genome

AF:

0.00349

AC:

531

AN:

152314

Hom.:

Cov.:

AF XY:

0.00325

AC XY:

242

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00560

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00495

Hom.:

Bravo

AF:

0.00334

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00149

AC:

ESP6500EA

AF:

0.00444

AC:

ExAC

AF:

0.00329

AC:

395

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DAAM2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 19, 2019

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

Labcorp Genetics (formerly Invitae), Labcorp

Mar 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

T;T;.;T;T

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.91

D;.;D;D;D

MetaRNN

Benign

0.0091

T;T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.4

.;L;L;L;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.040

.;N;N;N;N

REVEL

Uncertain

0.35

Sift

Benign

0.82

.;T;T;T;T

Sift4G

Benign

0.76

T;T;T;T;T

Polyphen

0.014, 1.0

.;B;.;B;D

Vest4

0.61

MutPred

0.51

Gain of phosphorylation at S20 (P = 0.1041);Gain of phosphorylation at S20 (P = 0.1041);Gain of phosphorylation at S20 (P = 0.1041);Gain of phosphorylation at S20 (P = 0.1041);Gain of phosphorylation at S20 (P = 0.1041);

MVP

0.71

MPC

0.51

ClinPred

0.024

GERP RS

6.1

Varity_R

0.084

gMVP

0.52

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