2-63056038-C-G

Variant names:

• chr2-63056038-C-G
• NM_014562.4:c.787C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014562.4(OTX1):​c.787C>G​(p.Gln263Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q263H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OTX1 NM_014562.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06
• Publications: 0 publications found

Genes affected

OTX1 (HGNC:8521): (orthodenticle homeobox 1) This gene encodes a member of the bicoid sub-family of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and may play a role in brain and sensory organ development. A similar protein in mouse is required for proper brain and sensory organ development and can cause epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2651068).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014562.4. 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
	OTX1	NM_014562.4	MANE Select	c.787C>G	p.Gln263Glu	missense	Exon 5 of 5	NP_055377.1	P32242
	OTX1	NM_001199770.2		c.787C>G	p.Gln263Glu	missense	Exon 5 of 5	NP_001186699.1	P32242
	OTX1	NR_130153.2		n.1150C>G		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTX1	ENST00000282549.7	TSL:1 MANE Select	c.787C>G	p.Gln263Glu	missense	Exon 5 of 5	ENSP00000282549.2	P32242
	OTX1	ENST00000366671.7	TSL:3	c.787C>G	p.Gln263Glu	missense	Exon 5 of 5	ENSP00000355631.3	P32242
	OTX1	ENST00000946233.1		c.787C>G	p.Gln263Glu	missense	Exon 5 of 5	ENSP00000616292.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D
Eigen	Benign	0.072
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.1
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.99	N
REVEL	Uncertain	0.44
Sift	Benign	0.091	T
Sift4G	Benign	0.94	T
Polyphen		0.63	P
Vest4		0.22
MutPred		0.45		Gain of phosphorylation at S265 (P = 0.14)
MVP		0.77
ClinPred		0.71	D
GERP RS		3.4
Varity_R		0.14
gMVP		0.57
Mutation Taster		=83/17	polymorphism

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

hg19: chr2-63283173;