chr2-63050708-C-G

Position:

• chr2-63050708-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001199770.2(OTX1):​c.-180-541C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,656 control chromosomes in the GnomAD database, including 17,464 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (17464 hom., cov: 31)
  • Exomes 𝑓: 0.64 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: OTX1 NM_001199770.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTX1	NM_001199770.2	c.-180-541C>G		intron_variant			NP_001186699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTX1	ENST00000366671.7	c.-180-541C>G		intron_variant		3		ENSP00000355631	P1
OTX1	ENST00000484066.2			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72154 AN: 151552 Hom.: 17460 Cov.: 31

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.478

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.643 AC: 9 AN: 14 Hom.: 2 Cov.: 0 AF XY: 0.700 AC XY: 7 AN XY: 10

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.667

GnomAD4 genome AF: 0.476 AC: 72180 AN: 151656 Hom.: 17464 Cov.: 31 AF XY: 0.476 AC XY: 35299 AN XY: 74098

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.480

Alfa AF: 0.341 Hom.: 870

Bravo AF: 0.484

Asia WGS AF: 0.668 AC: 2302 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs58235267; hg19: chr2-63277843;