chr13-105474537-A-G

Variant names:

• chr13-105474537-A-G
• rs10492528
• NM_172370.5:c.281+1852A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172370.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAOA	NM_172370.5	MANE Select	c.281+1852A>G		intron	N/A	NP_758958.3
	DAOA	NM_001384644.1		c.282-440A>G		intron	N/A	NP_001371573.1
	DAOA	NM_001161812.1		c.88+1852A>G		intron	N/A	NP_001155284.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAOA	ENST00000375936.9	TSL:1 MANE Select	c.281+1852A>G		intron	N/A	ENSP00000365103.3
	DAOA	ENST00000595812.2	TSL:1	c.88+1852A>G		intron	N/A	ENSP00000469539.1
	DAOA	ENST00000329625.9	TSL:1	c.68+1852A>G		intron	N/A	ENSP00000329951.5

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

African (AFR) AF: 0.168 AC: 6972 AN: 41514

American (AMR) AF: 0.147 AC: 2249 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 474 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5186

South Asian (SAS) AF: 0.0739 AC: 357 AN: 4830

European-Finnish (FIN) AF: 0.132 AC: 1400 AN: 10588

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11709 AN: 67968

Other (OTH) AF: 0.159 AC: 335 AN: 2112

Alfa AF: 0.161 Hom.: 1182

Bravo AF: 0.160

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.14
DANN	Benign	0.40
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10492528; hg19: chr13-106126886;