12-108894208-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001917.5(DAO):c.508-55A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,319,388 control chromosomes in the GnomAD database, including 28,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3620 hom., cov: 31)
  • Exomes 𝑓: 0.18 (24717 hom.)
• Consequence: DAO NM_001917.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.12

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]

LOC124903011 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 12-108894208-A-G is Benign according to our data. Variant chr12-108894208-A-G is described in ClinVar as [Benign]. Clinvar id is 1269904.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAO	NM_001917.5	c.508-55A>G		intron_variant		ENST00000228476.8
LOC124903011	XR_007063453.1	n.520-380T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAO	ENST00000228476.8	c.508-55A>G		intron_variant		1	NM_001917.5	P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28957 AN: 151898 Hom.: 3619 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.185 AC: 215835 AN: 1167372 Hom.: 24717 AF XY: 0.185 AC XY: 109193 AN XY: 590556

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.490

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.472

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.191 AC: 28983 AN: 152016 Hom.: 3620 Cov.: 31 AF XY: 0.201 AC XY: 14973 AN XY: 74324

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.227

Alfa AF: 0.165 Hom.: 1112

Bravo AF: 0.204

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.039
Dann	Benign	0.47

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: rs3825251; hg19: chr12-109287984; COSMIC: COSV57325441; COSMIC: COSV57325441;