Genetic Variant DAOA:c.282-255T>C (chr13-105489646-T-C) – 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.282-255T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 799,876 control chromosomes in the GnomAD database, including 81,367 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 0.50 ( 20257 hom., cov: 33)

Exomes 𝑓: 0.43 ( 61110 hom. )

Consequence

DAOA
NM_172370.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33

Publications

9 publications found

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 (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAOA	NM_172370.5 link	c.282-255T>C		intron_variant	Intron 4 of 5	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.282-255T>C		intron_variant	Intron 4 of 5	1	NM_172370.5	ENSP00000365103.3		P59103-1
DAOA	ENST00000471432.3 link	n.*393-146T>C		intron_variant	Intron 5 of 6	1		ENSP00000472857.1		M0R2W9

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

76040

AN:

151968

Hom.:

20229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.687

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.463

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.430

Gnomad OTH

AF:

0.477

GnomAD4 exome

AF:

0.429

AC:

278175

AN:

647790

Hom.:

61110

AF XY:

0.426

AC XY:

139350

AN XY:

327398

show subpopulations

African (AFR)

AF:

0.694

AC:

11313

AN:

16312

American (AMR)

AF:

0.437

AC:

7851

AN:

17960

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

6238

AN:

14052

East Asian (EAS)

AF:

0.354

AC:

11016

AN:

31094

South Asian (SAS)

AF:

0.376

AC:

15697

AN:

41758

European-Finnish (FIN)

AF:

0.440

AC:

12349

AN:

28074

Middle Eastern (MID)

AF:

0.394

AC:

908

AN:

2304

European-Non Finnish (NFE)

AF:

0.428

AC:

198679

AN:

464350

Other (OTH)

AF:

0.443

AC:

14124

AN:

31886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

7365

14730

22096

29461

36826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4532

9064

13596

18128

22660

<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:

0.501

AC:

76121

AN:

152086

Hom.:

20257

Cov.:

AF XY:

0.495

AC XY:

36825

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.688

AC:

28525

AN:

41490

American (AMR)

AF:

0.440

AC:

6723

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.437

AC:

1518

AN:

3472

East Asian (EAS)

AF:

0.368

AC:

1894

AN:

5146

South Asian (SAS)

AF:

0.380

AC:

1829

AN:

4816

European-Finnish (FIN)

AF:

0.463

AC:

4903

AN:

10582

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.430

AC:

29202

AN:

67974

Other (OTH)

AF:

0.476

AC:

1006

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1878

3757

5635

7514

9392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.448

Hom.:

26201

Bravo

AF:

0.510

Asia WGS

AF:

0.409

AC:

1425

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.92

(source)

DANN

Benign

0.42

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over