12-108884971-T-G

Variant names:

• chr12-108884971-T-G
• rs2111902
• NM_001917.5:c.-9-27T>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.-9-27T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,603,824 control chromosomes in the GnomAD database, including 98,144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13550 hom., cov: 32)
  • Exomes 𝑓: 0.33 (84594 hom.)
• Consequence: DAO NM_001917.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.557
• Publications: 25 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=-0.89).
• BP6: Variant 12-108884971-T-G is Benign according to our data. Variant chr12-108884971-T-G is described in ClinVar as Benign. ClinVar VariationId is 1243869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAO	NM_001917.5	c.-9-27T>G		intron_variant	Intron 1 of 10	ENST00000228476.8	NP_001908.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAO	ENST00000228476.8	c.-9-27T>G		intron_variant	Intron 1 of 10	1	NM_001917.5	ENSP00000228476.3

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61210 AN: 151816 Hom.: 13516 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.429

GnomAD2 exomes AF: 0.398 AC: 99716 AN: 250800 AF XY: 0.390

Gnomad AFR exome AF: 0.546

Gnomad AMR exome AF: 0.603

Gnomad ASJ exome AF: 0.376

Gnomad EAS exome AF: 0.501

Gnomad FIN exome AF: 0.326

Gnomad NFE exome AF: 0.295

Gnomad OTH exome AF: 0.375

GnomAD4 exome AF: 0.330 AC: 478983 AN: 1451890 Hom.: 84594 Cov.: 30 AF XY: 0.333 AC XY: 240568 AN XY: 723068

African (AFR) AF: 0.561 AC: 18655 AN: 33280

American (AMR) AF: 0.595 AC: 26584 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 9681 AN: 26082

East Asian (EAS) AF: 0.478 AC: 18952 AN: 39634

South Asian (SAS) AF: 0.469 AC: 40392 AN: 86068

European-Finnish (FIN) AF: 0.316 AC: 16818 AN: 53268

Middle Eastern (MID) AF: 0.461 AC: 2652 AN: 5756

European-Non Finnish (NFE) AF: 0.294 AC: 323819 AN: 1103084

Other (OTH) AF: 0.357 AC: 21430 AN: 60016

GnomAD4 genome AF: 0.404 AC: 61310 AN: 151934 Hom.: 13550 Cov.: 32 AF XY: 0.411 AC XY: 30537 AN XY: 74262

African (AFR) AF: 0.548 AC: 22684 AN: 41394

American (AMR) AF: 0.534 AC: 8150 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1291 AN: 3468

East Asian (EAS) AF: 0.491 AC: 2537 AN: 5170

South Asian (SAS) AF: 0.470 AC: 2264 AN: 4816

European-Finnish (FIN) AF: 0.333 AC: 3513 AN: 10562

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19565 AN: 67964

Other (OTH) AF: 0.432 AC: 911 AN: 2110

Alfa AF: 0.320 Hom.: 22090

Bravo AF: 0.427

Asia WGS AF: 0.449 AC: 1563 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	-0.89
CADD	Benign	2.4
DANN	Benign	0.62
PhyloP100		-0.56
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: rs2111902; hg19: chr12-109278747; COSMIC: COSV57321782; COSMIC: COSV57321782;