Genetic Variant DAOA:c.281+2495C>T (chr13-105475180-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_172370.5(DAOA):c.281+2495C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 301,528 control chromosomes in the GnomAD database, including 14,675 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 0.31 ( 7178 hom., cov: 32)

Exomes 𝑓: 0.32 ( 7497 hom. )

Consequence

DAOA
NM_172370.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.717

Publications

8 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAOA	NM_172370.5 link	c.281+2495C>T		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.281+2495C>T		intron_variant	Intron 4 of 5	1	NM_172370.5	ENSP00000365103.3		P59103-1
DAOA	ENST00000471432.3 link	n.*296+110C>T		intron_variant	Intron 4 of 6	1		ENSP00000472857.1		M0R2W9

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46640

AN:

151892

Hom.:

7174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.324

GnomAD4 exome

AF:

0.317

AC:

47400

AN:

149516

Hom.:

7497

AF XY:

0.321

AC XY:

23090

AN XY:

71988

show subpopulations

African (AFR)

AF:

0.342

AC:

905

AN:

2646

American (AMR)

AF:

0.247

AC:

AN:

174

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

300

AN:

910

East Asian (EAS)

AF:

0.236

AC:

147

AN:

622

South Asian (SAS)

AF:

0.326

AC:

955

AN:

2932

European-Finnish (FIN)

AF:

0.250

AC:

AN:

144

Middle Eastern (MID)

AF:

0.356

AC:

101

AN:

284

European-Non Finnish (NFE)

AF:

0.317

AC:

43349

AN:

136946

Other (OTH)

AF:

0.322

AC:

1564

AN:

4858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1666

3332

4998

6664

8330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1958

3916

5874

7832

9790

<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:

0.307

AC:

46654

AN:

152012

Hom.:

7178

Cov.:

AF XY:

0.304

AC XY:

22588

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.326

AC:

13529

AN:

41492

American (AMR)

AF:

0.290

AC:

4434

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1093

AN:

3464

East Asian (EAS)

AF:

0.223

AC:

1147

AN:

5150

South Asian (SAS)

AF:

0.311

AC:

1500

AN:

4818

European-Finnish (FIN)

AF:

0.247

AC:

2606

AN:

10566

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.313

AC:

21231

AN:

67916

Other (OTH)

AF:

0.323

AC:

682

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1643

3286

4929

6572

8215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<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:

0.311

Hom.:

4907

Bravo

AF:

0.310

Asia WGS

AF:

0.280

AC:

974

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

0.72

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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