Variant rs2391191 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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 same amino acid change has been previously reported as Likely benignin 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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DAOA	NM_172370.5 linkuse as main transcript	c.89G>A	p.Arg30Lys	missense_variant	3/6	ENST00000375936.9	NP_758958.3
DAOA-AS1	NR_040247.1 linkuse as main transcript	n.506-677C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAOA	ENST00000375936.9 linkuse as main transcript	c.89G>A	p.Arg30Lys	missense_variant	3/6	1	NM_172370.5	ENSP00000365103	P2	P59103-1
DAOA-AS1	ENST00000448407.1 linkuse as main transcript	n.506-677C>T		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes

AF:

0.395

AC:

97727

AN:

247340

Hom.:

20756

AF XY:

0.396

AC XY:

53198

AN XY:

134294

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 SAS exome

AF:

0.406

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

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.439

Gnomad4 ASJ exome

AF:

0.335

Gnomad4 EAS exome

AF:

0.681

Gnomad4 SAS exome

AF:

0.412

Gnomad4 FIN exome

AF:

0.436

Gnomad4 NFE exome

AF:

0.385

Gnomad4 OTH exome

AF:

0.372

GnomAD4 genome

AF:

0.323

AC:

49057

AN:

151948

Hom.:

9375

Cov.:

AF XY:

0.330

AC XY:

24534

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.391

Gnomad4 ASJ

AF:

0.354

Gnomad4 EAS

AF:

0.631

Gnomad4 SAS

AF:

0.424

Gnomad4 FIN

AF:

0.437

Gnomad4 NFE

AF:

0.383

Gnomad4 OTH

AF:

0.328

Alfa

AF:

0.371

Hom.:

20541

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

not provided, no classification provided

literature only

Psychiatry Genetics Yale University

- -

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

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

MutationTaster

Benign

1.0

P;P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over