rs12862108

Positions:

• chr13-105473859-C-A
• chr13-105473859-C-G
• chr13-105473859-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172370.5(DAOA):​c.281+1174C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,958 control chromosomes in the GnomAD database, including 5,877 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 0.28 (5877 hom., cov: 32)
• Consequence: DAOA NM_172370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAOA	NM_172370.5	c.281+1174C>A		intron_variant		ENST00000375936.9
DAOA-AS1	NR_040247.1	n.506-7439G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAOA	ENST00000375936.9	c.281+1174C>A		intron_variant		1	NM_172370.5	P2
DAOA-AS1	ENST00000448407.1	n.506-7439G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41783 AN: 151840 Hom.: 5868 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.264

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.275 AC: 41821 AN: 151958 Hom.: 5877 Cov.: 32 AF XY: 0.273 AC XY: 20283 AN XY: 74252

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.263

Alfa AF: 0.156 Hom.: 303

Bravo AF: 0.273

Asia WGS AF: 0.191 AC: 666 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.85

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

LitVar

Other links and lift over

dbSNP: rs12862108; hg19: chr13-106126208;