Genetic Variant DAAM2:p.His9His (chr6-39856329-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001201427.2(DAAM2):c.27T>C(p.His9His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,548,998 control chromosomes in the GnomAD database, including 288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 20 hom., cov: 32)

Exomes 𝑓: 0.014 ( 268 hom. )

Consequence

DAAM2
NM_001201427.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.61

Publications

6 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=-0.52).

BP6

Variant 6-39856329-T-C is Benign according to our data. Variant chr6-39856329-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060337.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.61 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM2	NM_001201427.2 link	c.27T>C	p.His9His	synonymous_variant	Exon 2 of 25	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.27T>C	p.His9His	synonymous_variant	Exon 2 of 25	1	NM_001201427.2	ENSP00000274867.4		Q86T65-3

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1859

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00536

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.0591

Gnomad SAS

AF:

0.00973

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0139

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.0135

AC:

2240

AN:

165822

AF XY:

0.0138

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.00854

Gnomad EAS exome

AF:

0.0569

Gnomad FIN exome

AF:

0.00454

Gnomad NFE exome

AF:

0.0139

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.0142

AC:

19792

AN:

1396676

Hom.:

268

Cov.:

AF XY:

0.0140

AC XY:

9690

AN XY:

690098

show subpopulations

African (AFR)

AF:

0.00566

AC:

176

AN:

31100

American (AMR)

AF:

0.00989

AC:

357

AN:

36108

Ashkenazi Jewish (ASJ)

AF:

0.00772

AC:

187

AN:

24214

East Asian (EAS)

AF:

0.0756

AC:

2639

AN:

34898

South Asian (SAS)

AF:

0.00695

AC:

532

AN:

76564

European-Finnish (FIN)

AF:

0.00530

AC:

268

AN:

50610

Middle Eastern (MID)

AF:

0.0432

AC:

241

AN:

5580

European-Non Finnish (NFE)

AF:

0.0135

AC:

14549

AN:

1079664

Other (OTH)

AF:

0.0146

AC:

843

AN:

57938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1048

2096

3145

4193

5241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

572

1144

1716

2288

2860

<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:

0.0122

AC:

1859

AN:

152322

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

880

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00539

AC:

224

AN:

41578

American (AMR)

AF:

0.0146

AC:

224

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3470

East Asian (EAS)

AF:

0.0591

AC:

306

AN:

5180

South Asian (SAS)

AF:

0.00973

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00452

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0139

AC:

944

AN:

68020

Other (OTH)

AF:

0.0132

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

193

289

386

482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00999

Hom.:

Bravo

AF:

0.0124

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DAAM2-related disorder

Benign:1

Feb 19, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.5

(source)

DANN

Benign

0.62

PhyloP100

2.6

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over