dbSNP rs2504082: DAAM2:c.1846-59A>G (chr6-39883903-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001201427.2(DAAM2):c.1846-59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,100,156 control chromosomes in the GnomAD database, including 102,470 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 15273 hom., cov: 31)

Exomes 𝑓: 0.42 ( 87197 hom. )

Consequence

DAAM2
NM_001201427.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00800

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM2	NM_001201427.2 link	c.1846-59A>G		intron_variant	Intron 14 of 24	ENST00000274867.9	NP_001188356.1	Q86T65-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM2	ENST00000274867.9 link	c.1846-59A>G		intron_variant	Intron 14 of 24	1	NM_001201427.2	ENSP00000274867.4		Q86T65-3

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

66998

AN:

151764

Hom.:

15248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.526

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.415

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.366

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.437

GnomAD4 exome

AF:

0.423

AC:

401446

AN:

948270

Hom.:

87197

Cov.:

AF XY:

0.420

AC XY:

205378

AN XY:

489078

show subpopulations

African (AFR)

AF:

0.523

AC:

12429

AN:

23754

American (AMR)

AF:

0.430

AC:

16847

AN:

39218

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

9311

AN:

22286

East Asian (EAS)

AF:

0.259

AC:

9464

AN:

36486

South Asian (SAS)

AF:

0.326

AC:

23450

AN:

71920

European-Finnish (FIN)

AF:

0.346

AC:

17816

AN:

51562

Middle Eastern (MID)

AF:

0.399

AC:

1863

AN:

4664

European-Non Finnish (NFE)

AF:

0.446

AC:

292304

AN:

655022

Other (OTH)

AF:

0.414

AC:

17962

AN:

43358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

11476

22953

34429

45906

57382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6794

13588

20382

27176

33970

<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:

0.442

AC:

67065

AN:

151886

Hom.:

15273

Cov.:

AF XY:

0.434

AC XY:

32191

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.526

AC:

21771

AN:

41402

American (AMR)

AF:

0.441

AC:

6726

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

1440

AN:

3470

East Asian (EAS)

AF:

0.217

AC:

1121

AN:

5156

South Asian (SAS)

AF:

0.326

AC:

1569

AN:

4806

European-Finnish (FIN)

AF:

0.319

AC:

3358

AN:

10542

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.439

AC:

29841

AN:

67934

Other (OTH)

AF:

0.433

AC:

915

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1902

3804

5707

7609

9511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<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:

0.436

Hom.:

24015

Bravo

AF:

0.452

Asia WGS

AF:

0.287

AC:

997

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.3

(source)

DANN

Benign

0.52

PhyloP100

0.0080

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over