12-108894208-A-G

Variant names:

• chr12-108894208-A-G
• rs3825251
• NM_001917.5:c.508-55A>G

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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.12
• Publications: 17 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

LOC124903011 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1269904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAO	NM_001917.5	c.508-55A>G		intron_variant	Intron 6 of 10	ENST00000228476.8	NP_001908.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAO	ENST00000228476.8	c.508-55A>G		intron_variant	Intron 6 of 10	1	NM_001917.5	ENSP00000228476.3

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

African (AFR) AF: 0.127 AC: 3513 AN: 27712

American (AMR) AF: 0.490 AC: 19291 AN: 39402

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 4494 AN: 23888

East Asian (EAS) AF: 0.472 AC: 17277 AN: 36632

South Asian (SAS) AF: 0.219 AC: 16839 AN: 76990

European-Finnish (FIN) AF: 0.212 AC: 10817 AN: 50916

Middle Eastern (MID) AF: 0.227 AC: 1049 AN: 4622

European-Non Finnish (NFE) AF: 0.155 AC: 132628 AN: 856628

Other (OTH) AF: 0.196 AC: 9927 AN: 50582

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

African (AFR) AF: 0.128 AC: 5297 AN: 41464

American (AMR) AF: 0.404 AC: 6158 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3470

East Asian (EAS) AF: 0.477 AC: 2458 AN: 5152

South Asian (SAS) AF: 0.232 AC: 1118 AN: 4824

European-Finnish (FIN) AF: 0.220 AC: 2325 AN: 10590

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.152 AC: 10347 AN: 67944

Other (OTH) AF: 0.227 AC: 479 AN: 2110

Alfa AF: 0.164 Hom.: 1232

Bravo AF: 0.204

Asia WGS AF: 0.296 AC: 1030 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.039
DANN	Benign	0.47
PhyloP100		-2.1
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: rs3825251; hg19: chr12-109287984; COSMIC: COSV57325441; COSMIC: COSV57325441;