Variant 6-39867596-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000274867.9(DAAM2):c.515G>A(p.Arg172His) variant causes a missense change. The variant allele was found at a frequency of 0.00301 in 1,613,992 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R172C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 18 hom. )

Consequence

DAAM2
ENST00000274867.9 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.22

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011351585).

BP6

Variant 6-39867596-G-A is Benign according to our data. Variant chr6-39867596-G-A is described in ClinVar as [Benign]. Clinvar id is 3039245.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM2	NM_001201427.2 linkuse as main transcript	c.515G>A	p.Arg172His	missense_variant	6/25	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.515G>A	p.Arg172His	missense_variant	6/25	1	NM_001201427.2	ENSP00000274867	P1	Q86T65-3

Frequencies

GnomAD3 genomes

AF:

0.00194

AC:

295

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00262

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00204

AC:

507

AN:

249104

Hom.:

AF XY:

0.00212

AC XY:

286

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.00283

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.00312

AC:

4561

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

2201

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.00353

Gnomad4 OTH exome

AF:

0.00366

GnomAD4 genome

AF:

0.00194

AC:

295

AN:

152282

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00260

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00305

Hom.:

Bravo

AF:

0.00241

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00247

AC:

ExAC

AF:

0.00185

AC:

224

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DAAM2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.10

T;D;.;D

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.83

LIST_S2

Pathogenic

0.97

D;.;D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Uncertain

0.18

MutationAssessor

Benign

2.0

.;M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.4

.;N;N;N

REVEL

Uncertain

0.57

Sift

Benign

0.035

.;D;D;D

Sift4G

Benign

0.14

T;T;T;T

Polyphen

0.98

.;D;.;D

Vest4

0.42

MVP

0.73

MPC

0.70

ClinPred

0.32

GERP RS

4.5

Varity_R

0.15

gMVP

0.50

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