Variant 6-39864488-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The ENST00000274867.9(DAAM2):c.314G>A(p.Arg105His) variant causes a missense change. The variant allele was found at a frequency of 0.00118 in 1,611,824 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R105C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0046 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 7 hom. )

Consequence

DAAM2
ENST00000274867.9 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.29

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0097029805).

BP6

Variant 6-39864488-G-A is Benign according to our data. Variant chr6-39864488-G-A is described in ClinVar as [Benign]. Clinvar id is 3039055.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000819 (1195/1459632) while in subpopulation AFR AF= 0.0168 (563/33424). AF 95% confidence interval is 0.0157. There are 7 homozygotes in gnomad4_exome. There are 569 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM2	NM_001201427.2 linkuse as main transcript	c.314G>A	p.Arg105His	missense_variant	4/25	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.314G>A	p.Arg105His	missense_variant	4/25	1	NM_001201427.2	ENSP00000274867	P1	Q86T65-3

Frequencies

GnomAD3 genomes

AF:

0.00458

AC:

697

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00172

AC:

425

AN:

246724

Hom.:

AF XY:

0.00135

AC XY:

180

AN XY:

133800

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.00178

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000664

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000241

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000819

AC:

1195

AN:

1459632

Hom.:

Cov.:

AF XY:

0.000784

AC XY:

569

AN XY:

725962

show subpopulations

Gnomad4 AFR exome

AF:

0.0168

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.00931

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000582

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000155

Gnomad4 OTH exome

AF:

0.00191

GnomAD4 genome

AF:

0.00462

AC:

703

AN:

152192

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

320

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0146

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00135

Hom.:

Bravo

AF:

0.00524

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0125

AC:

ESP6500EA

AF:

0.000838

AC:

ExAC

AF:

0.00169

AC:

205

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000238

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

May 24, 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

0.19

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.25

T;D;.;D

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

D;.;D;D

MetaRNN

Benign

0.0097

T;T;T;T

MetaSVM

Uncertain

0.53

MutationAssessor

Benign

1.8

.;L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.9

.;D;D;D

REVEL

Uncertain

0.59

Sift

Uncertain

0.0040

.;D;D;D

Sift4G

Uncertain

0.023

D;D;D;D

Polyphen

1.0

.;D;.;D

Vest4

0.52

MVP

0.74

MPC

0.72

ClinPred

0.034

GERP RS

5.9

Varity_R

0.35

gMVP

0.61

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