rs2070587

Variant names:

• chr12-108883967-T-G
• rs2070587
• NM_001917.5:c.-9-1031T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001917.5(DAO):​c.-9-1031T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,214 control chromosomes in the GnomAD database, including 9,710 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 0.32 (9710 hom., cov: 33)
• Consequence: DAO NM_001917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 13 publications found

Genes affected

DAO (HGNC:2671): (D-amino acid oxidase) This gene encodes the peroxisomal enzyme D-amino acid oxidase. The enzyme is a flavoprotein which uses flavin adenine dinucleotide (FAD) as its prosthetic group. Its substrates include a wide variety of D-amino acids, but it is inactive on the naturally occurring L-amino acids. Its biological function is not known; it may act as a detoxifying agent which removes D-amino acids that accumulate during aging. In mice, it degrades D-serine, a co-agonist of the NMDA receptor. This gene may play a role in the pathophysiology of schizophrenia. [provided by RefSeq, Jul 2008]

DAO Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001917.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAO	NM_001917.5	MANE Select	c.-9-1031T>G		intron	N/A	NP_001908.3
	DAO	NM_001413634.1		c.-9-1031T>G		intron	N/A	NP_001400563.1	P14920
	DAO	NM_001413635.1		c.-9-1031T>G		intron	N/A	NP_001400564.1	A0A0S2Z3J4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAO	ENST00000228476.8	TSL:1 MANE Select	c.-9-1031T>G		intron	N/A	ENSP00000228476.3	P14920
	DAO	ENST00000551281.5	TSL:1	c.-9-1031T>G		intron	N/A	ENSP00000446853.1	A0A0B4J250
	DAO	ENST00000547122.5	TSL:1	n.-9-1031T>G		intron	N/A	ENSP00000448095.1	A0A0B4J257

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48849 AN: 152096 Hom.: 9689 Cov.: 33

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.322 AC: 48937 AN: 152214 Hom.: 9710 Cov.: 33 AF XY: 0.327 AC XY: 24339 AN XY: 74420

African (AFR) AF: 0.526 AC: 21852 AN: 41516

American (AMR) AF: 0.437 AC: 6675 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3472

East Asian (EAS) AF: 0.334 AC: 1732 AN: 5184

South Asian (SAS) AF: 0.336 AC: 1622 AN: 4832

European-Finnish (FIN) AF: 0.246 AC: 2603 AN: 10600

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12795 AN: 68008

Other (OTH) AF: 0.312 AC: 657 AN: 2108

Alfa AF: 0.236 Hom.: 8604

Bravo AF: 0.345

Asia WGS AF: 0.315 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.77
PhyloP100		1.2
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: rs2070587; hg19: chr12-109277743;