rs10492528

Positions:

• chr13-105474537-A-G

Variant summary

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

The NM_172370.5(DAOA):​c.281+1852A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,138 control chromosomes in the GnomAD database, including 1,954 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 0.16 (1954 hom., cov: 33)
• Consequence: DAOA NM_172370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAOA	NM_172370.5	c.281+1852A>G		intron_variant		ENST00000375936.9	NP_758958.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAOA	ENST00000375936.9	c.281+1852A>G		intron_variant		1	NM_172370.5	ENSP00000365103.3
DAOA	ENST00000471432.3	n.*203-440A>G		intron_variant		1		ENSP00000472857.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23726 AN: 152020 Hom.: 1953 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0743

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.156 AC: 23738 AN: 152138 Hom.: 1954 Cov.: 33 AF XY: 0.152 AC XY: 11290 AN XY: 74388

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0739

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.159

Alfa AF: 0.160 Hom.: 1042

Bravo AF: 0.160

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.14
DANN	Benign	0.40

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: rs10492528; hg19: chr13-106126886;