dbSNP rs2391191: DAOA:p.Arg30Lys (chr13-105467097-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_172370.5(DAOA):c.89G>A(p.Arg30Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,605,620 control chromosomes in the GnomAD database, including 124,517 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.32 ( 9375 hom., cov: 32)

Exomes 𝑓: 0.39 ( 115142 hom. )

Consequence

DAOA
NM_172370.5 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.143

Variant links:

Genes affected

DAOA (HGNC:21191): (D-amino acid oxidase activator) This gene encodes a protein that may function as an activator of D-amino acid oxidase, which degrades the gliotransmitter D-serine, a potent activator of N-methyl-D-aspartate (NMDA) type glutamate receptors. Studies also suggest that one encoded isoform may play a role in mitochondrial function and dendritic arborization. Polymorphisms in this gene have been implicated in susceptibility to schizophrenia and bipolar affective disorder. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Mar 2011]

DAOA links:

DAOA-AS1 (HGNC:30243): (DAOA antisense RNA 1)

DAOA-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.3847223E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAOA	NM_172370.5 link	c.89G>A	p.Arg30Lys	missense_variant	Exon 3 of 6	ENST00000375936.9	NP_758958.3	P59103-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAOA	ENST00000375936.9 link	c.89G>A	p.Arg30Lys	missense_variant	Exon 3 of 6	1	NM_172370.5	ENSP00000365103.3		P59103-1
DAOA	ENST00000471432.3 link	n.-14G>A		upstream_gene_variant		1		ENSP00000472857.1		M0R2W9

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49047

AN:

151828

Hom.:

9375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.391

Gnomad ASJ

AF:

0.354

Gnomad EAS

AF:

0.630

Gnomad SAS

AF:

0.425

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.327

GnomAD2 exomes

AF:

0.395

AC:

97727

AN:

247340

AF XY:

0.396

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.340

Gnomad EAS exome

AF:

0.617

Gnomad FIN exome

AF:

0.434

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.387

GnomAD4 exome

AF:

0.390

AC:

566856

AN:

1453672

Hom.:

115142

Cov.:

AF XY:

0.391

AC XY:

282615

AN XY:

723224

show subpopulations

African (AFR)

AF:

0.101

AC:

3385

AN:

33388

American (AMR)

AF:

0.439

AC:

19455

AN:

44360

Ashkenazi Jewish (ASJ)

AF:

0.335

AC:

8678

AN:

25894

East Asian (EAS)

AF:

0.681

AC:

26822

AN:

39372

South Asian (SAS)

AF:

0.412

AC:

35293

AN:

85560

European-Finnish (FIN)

AF:

0.436

AC:

23019

AN:

52832

Middle Eastern (MID)

AF:

0.309

AC:

1774

AN:

5736

European-Non Finnish (NFE)

AF:

0.385

AC:

426069

AN:

1106482

Other (OTH)

AF:

0.372

AC:

22361

AN:

60048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

16783

33566

50349

67132

83915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.323

AC:

49057

AN:

151948

Hom.:

9375

Cov.:

AF XY:

0.330

AC XY:

24534

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.115

AC:

4781

AN:

41464

American (AMR)

AF:

0.391

AC:

5980

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

1228

AN:

3470

East Asian (EAS)

AF:

0.631

AC:

3251

AN:

5156

South Asian (SAS)

AF:

0.424

AC:

2045

AN:

4818

European-Finnish (FIN)

AF:

0.437

AC:

4589

AN:

10510

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.383

AC:

26018

AN:

67934

Other (OTH)

AF:

0.328

AC:

692

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1560

3120

4680

6240

7800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.366

Hom.:

43319

Bravo

AF:

0.310

TwinsUK

AF:

0.378

AC:

1402

ALSPAC

AF:

0.385

AC:

1482

ESP6500AA

AF:

0.115

AC:

411

ESP6500EA

AF:

0.373

AC:

3026

ExAC

AF:

0.389

AC:

46962

Asia WGS

AF:

0.466

AC:

1614

AN:

3466

EpiCase

AF:

0.372

EpiControl

AF:

0.367

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

Psychiatry Genetics Yale University

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.4

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0052

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0064

LIST_S2

Benign

0.35

.;T

MetaRNN

Benign

0.0000074

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

N;N

PhyloP100

0.14

PROVEAN

Benign

-1.5

N;.

REVEL

Benign

0.062

Sift

Benign

0.76

T;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.40

B;B

Vest4

0.021

MPC

0.0032

ClinPred

0.0049

GERP RS

-0.30

Varity_R

0.039

gMVP

0.047

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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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rs2391191

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over