17-42844808-G-T

Variant names:

• chr17-42844808-G-T
• rs745478032
• NM_009590.4:c.182G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_009590.4(AOC2):​c.182G>T​(p.Arg61Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R61Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AOC2 NM_009590.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 2 publications found

Genes affected

AOC2 (HGNC:549): (amine oxidase copper containing 2) Copper amine oxidases catalyze the oxidative conversion of amines to aldehydes and ammonia in the presence of copper and quinone cofactor. This gene shows high sequence similarity to copper amine oxidases from various species ranging from bacteria to mammals. The protein contains several conserved motifs including the active site of amine oxidases and the histidine residues that likely bind copper. It may be a critical modulator of signal transmission in retina, possibly by degrading the biogenic amines dopamine, histamine, and putrescine. This gene may be a candidate gene for hereditary ocular diseases. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03389901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AOC2	NM_009590.4	c.182G>T	p.Arg61Leu	missense_variant	Exon 1 of 4	ENST00000253799.8	NP_033720.2
AOC2	NM_001158.5	c.182G>T	p.Arg61Leu	missense_variant	Exon 1 of 4		NP_001149.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AOC2	ENST00000253799.8	c.182G>T	p.Arg61Leu	missense_variant	Exon 1 of 4	1	NM_009590.4	ENSP00000253799.2
AOC2	ENST00000452774.2	c.182G>T	p.Arg61Leu	missense_variant	Exon 1 of 4	1		ENSP00000406134.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.5
DANN	Benign	0.64
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.034	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
PhyloP100		-2.0
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.044
Sift	Benign	0.23	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.0010	B;B
Vest4		0.22
MutPred		0.39		Loss of disorder (P = 0.0596);Loss of disorder (P = 0.0596);
MVP		0.17
MPC		0.028
ClinPred		0.12	T
GERP RS		-8.6
PromoterAI		-0.047	Neutral
Varity_R		0.086
gMVP		0.42

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: rs745478032; hg19: chr17-40996825;