rs546485721

Variant names:

• chr12-108885154-GGCCTCT-G
• rs546485721
• NM_001917.5:c.150_155delCCTCTG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 3P and 5B. PM4 PP3 BP6 BS2

The NM_001917.5(DAO):​c.150_155delCCTCTG​(p.Leu51_Trp52del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000337 in 1,613,386 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (1 hom.)
• Consequence: DAO NM_001917.5 disruptive_inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 9.98
• Publications: 0 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, ClinGen, Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001917.5.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BP6: Variant 12-108885154-GGCCTCT-G is Benign according to our data. Variant chr12-108885154-GGCCTCT-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3047478.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 39 AD gene.

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.150_155delCCTCTG	p.Leu51_Trp52del	disruptive_inframe_deletion	Exon 2 of 11	NP_001908.3
	DAO	NM_001413634.1		c.150_155delCCTCTG	p.Leu51_Trp52del	disruptive_inframe_deletion	Exon 3 of 12	NP_001400563.1	P14920
	DAO	NM_001413635.1		c.150_155delCCTCTG	p.Leu51_Trp52del	disruptive_inframe_deletion	Exon 2 of 10	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.150_155delCCTCTG	p.Leu51_Trp52del	disruptive_inframe_deletion	Exon 2 of 11	ENSP00000228476.3	P14920
	DAO	ENST00000551281.5	TSL:1	c.150_155delCCTCTG	p.Leu51_Trp52del	disruptive_inframe_deletion	Exon 2 of 8	ENSP00000446853.1	A0A0B4J250
	DAO	ENST00000547122.5	TSL:1	n.150_155delCCTCTG		non_coding_transcript_exon	Exon 2 of 10	ENSP00000448095.1	A0A0B4J257

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000773 AC: 194 AN: 251102 AF XY: 0.000980

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000346 AC: 505 AN: 1461138 Hom.: 1 AF XY: 0.000453 AC XY: 329 AN XY: 726732

African (AFR) AF: 0.0000299 AC: 1 AN: 33462

American (AMR) AF: 0.000582 AC: 26 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 37 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39670

South Asian (SAS) AF: 0.00408 AC: 352 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53256

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5764

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111526

Other (OTH) AF: 0.000514 AC: 31 AN: 60368

GnomAD4 genome AF: 0.000256 AC: 39 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74448

African (AFR) AF: 0.00 AC: 0 AN: 41550

American (AMR) AF: 0.000654 AC: 10 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000391 Hom.: 0

Bravo AF: 0.000178

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DAO-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10
Mutation Taster		=129/71	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs546485721; hg19: chr12-109278930;