rs2070588

Variant names:

• chr12-108884393-C-G
• rs2070588
• NM_001917.5:c.-9-605C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001917.5(DAO):​c.-9-605C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,046 control chromosomes in the GnomAD database, including 11,874 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 0.37 (11874 hom., cov: 32)
• Consequence: DAO NM_001917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 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.-9-605C>G		intron	N/A	NP_001908.3
	DAO	NM_001413634.1		c.-9-605C>G		intron	N/A	NP_001400563.1	P14920
	DAO	NM_001413635.1		c.-9-605C>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.-9-605C>G		intron	N/A	ENSP00000228476.3	P14920
	DAO	ENST00000551281.5	TSL:1	c.-9-605C>G		intron	N/A	ENSP00000446853.1	A0A0B4J250
	DAO	ENST00000547122.5	TSL:1	n.-9-605C>G		intron	N/A	ENSP00000448095.1	A0A0B4J257

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55857 AN: 151928 Hom.: 11846 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.368 AC: 55953 AN: 152046 Hom.: 11874 Cov.: 32 AF XY: 0.376 AC XY: 27921 AN XY: 74332

African (AFR) AF: 0.541 AC: 22399 AN: 41430

American (AMR) AF: 0.495 AC: 7560 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1088 AN: 3472

East Asian (EAS) AF: 0.493 AC: 2546 AN: 5168

South Asian (SAS) AF: 0.439 AC: 2115 AN: 4816

European-Finnish (FIN) AF: 0.290 AC: 3070 AN: 10576

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 16012 AN: 67992

Other (OTH) AF: 0.385 AC: 810 AN: 2106

Alfa AF: 0.297 Hom.: 1006

Bravo AF: 0.392

Asia WGS AF: 0.435 AC: 1514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.8
DANN	Benign	0.41
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: rs2070588; hg19: chr12-109278169; COSMIC: COSV57323754; COSMIC: COSV57323754;