chr6-39864488-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001201427.2(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 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
NM_001201427.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.29

Publications

9 publications found

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:

DAAM2-AS1 (HGNC:40830): (DAAM2 antisense RNA 1)

DAAM2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3039055.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 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 GnomAdExome4. There are 569 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201427.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	NM_001201427.2	MANE Select	c.314G>A	p.Arg105His	missense	Exon 4 of 25	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.314G>A	p.Arg105His	missense	Exon 4 of 25	NP_056160.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DAAM2	ENST00000274867.9	TSL:1 MANE Select	c.314G>A	p.Arg105His	missense	Exon 4 of 25	ENSP00000274867.4	Q86T65-3
DAAM2	ENST00000538976.5	TSL:1	c.314G>A	p.Arg105His	missense	Exon 4 of 25	ENSP00000437808.1	Q86T65-4
DAAM2	ENST00000491083.2	TSL:1	n.460G>A		non_coding_transcript_exon	Exon 4 of 14

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

GnomAD2 exomes

AF:

0.00172

AC:

425

AN:

246724

AF XY:

0.00135

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 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

African (AFR)

AF:

0.0168

AC:

563

AN:

33424

American (AMR)

AF:

0.00188

AC:

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.00931

AC:

243

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000582

AC:

AN:

85852

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53322

Middle Eastern (MID)

AF:

0.00241

AC:

AN:

4982

European-Non Finnish (NFE)

AF:

0.000155

AC:

172

AN:

1111432

Other (OTH)

AF:

0.00191

AC:

115

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

113

170

226

283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00462

AC:

703

AN:

152192

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

320

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0146

AC:

608

AN:

41522

American (AMR)

AF:

0.00255

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68010

Other (OTH)

AF:

0.00284

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00217

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

ClinVar submissions as Germline

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

DAAM2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.25

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0097

MetaSVM

Uncertain

0.53

MutationAssessor

Benign

1.8

PhyloP100

4.3

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.59

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.023

Polyphen

1.0

Vest4

0.52

MVP

0.74

MPC

0.72

ClinPred

0.034

GERP RS

5.9

Varity_R

0.35

gMVP

0.61

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