chr12-108892800-G-C

Variant names:

• chr12-108892800-G-C
• rs11114087
• NM_001917.5:c.453-182G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001917.5(DAO):​c.453-182G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,122 control chromosomes in the GnomAD database, including 3,629 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.19 (3629 hom., cov: 31)
• Consequence: DAO NM_001917.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25
• Publications: 2 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: ClinGen, Orphanet, Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-108892800-G-C is Benign according to our data. Variant chr12-108892800-G-C is described in ClinVar as [Benign]. Clinvar id is 1278213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAO	NM_001917.5	c.453-182G>C		intron_variant	Intron 5 of 10	ENST00000228476.8	NP_001908.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAO	ENST00000228476.8	c.453-182G>C		intron_variant	Intron 5 of 10	1	NM_001917.5	ENSP00000228476.3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28999 AN: 152004 Hom.: 3628 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.191 AC: 29025 AN: 152122 Hom.: 3629 Cov.: 31 AF XY: 0.201 AC XY: 14984 AN XY: 74366

African (AFR) AF: 0.128 AC: 5325 AN: 41514

American (AMR) AF: 0.404 AC: 6170 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 654 AN: 3470

East Asian (EAS) AF: 0.478 AC: 2464 AN: 5160

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4814

European-Finnish (FIN) AF: 0.219 AC: 2315 AN: 10584

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.152 AC: 10355 AN: 67980

Other (OTH) AF: 0.227 AC: 479 AN: 2114

Alfa AF: 0.163 Hom.: 332

Bravo AF: 0.204

Asia WGS AF: 0.296 AC: 1028 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.18
DANN	Benign	0.57
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11114087; hg19: chr12-109286576; COSMIC: COSV57322066;