Genetic Variant DAAM2:c.429-10T>C (chr6-39867500-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001201427.2(DAAM2):c.429-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,612,252 control chromosomes in the GnomAD database, including 215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 114 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 101 hom. )

Consequence

DAAM2
NM_001201427.2 intron

Scores

Splicing: ADA: 0.001574

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.708

Publications

0 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 6-39867500-T-C is Benign according to our data. Variant chr6-39867500-T-C is described in ClinVar as Benign. ClinVar VariationId is 783753.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0704 is higher than 0.05.

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.429-10T>C		intron	N/A	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.429-10T>C		intron	N/A	NP_056160.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DAAM2	ENST00000274867.9	TSL:1 MANE Select	c.429-10T>C	intron	N/A	ENSP00000274867.4	Q86T65-3
DAAM2	ENST00000538976.5	TSL:1	c.429-10T>C	intron	N/A	ENSP00000437808.1	Q86T65-4
DAAM2	ENST00000491083.2	TSL:1	n.575-10T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0211

AC:

3207

AN:

152198

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0728

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.00561

AC:

1389

AN:

247386

AF XY:

0.00430

show subpopulations

Gnomad AFR exome

AF:

0.0794

Gnomad AMR exome

AF:

0.00362

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000189

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00212

AC:

3095

AN:

1459936

Hom.:

101

Cov.:

AF XY:

0.00187

AC XY:

1359

AN XY:

725938

show subpopulations

African (AFR)

AF:

0.0744

AC:

2490

AN:

33456

American (AMR)

AF:

0.00416

AC:

186

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.000104

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000138

AC:

153

AN:

1110338

Other (OTH)

AF:

0.00403

AC:

243

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

175

351

526

702

877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<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:

0.0211

AC:

3207

AN:

152316

Hom.:

114

Cov.:

AF XY:

0.0206

AC XY:

1531

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0725

AC:

3014

AN:

41554

American (AMR)

AF:

0.00915

AC:

140

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000367

AC:

AN:

68028

Other (OTH)

AF:

0.0128

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

152

303

455

606

758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0138

Hom.:

Bravo

AF:

0.0246

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.9

(source)

DANN

Benign

0.76

PhyloP100

0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0016

dbscSNV1_RF

Benign

0.11

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