rs3748492

chr20-18012625-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000486776.5(OVOL2):n.300-15873G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,168 control chromosomes in the GnomAD database, including 26,501 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 0.59 (26501 hom., cov: 34)
• Consequence: OVOL2 ENST00000486776.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

Genes affected

OVOL2 (HGNC:15804): (ovo like zinc finger 2) This gene encodes a member of the evolutionarily conserved ovo-like protein family. Mammalian members of this family contain a single zinc finger domain composed of a tetrad of C2H2 zinc fingers with variable N- and C-terminal extensions that contain intrinsically disordered domains. Members of this family are involved in epithelial development and differentiation. Knockout of this gene in mouse results in early embryonic lethality with phenotypes that include neurectoderm expansion, impaired vascularization, and heart anomalies. In humans, allelic variants of this gene have been associated with posterior polymorphous corneal dystrophy. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OVOL2	ENST00000486776.5	n.300-15873G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89131 AN: 152050 Hom.: 26460 Cov.: 34

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.588

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.586 AC: 89215 AN: 152168 Hom.: 26501 Cov.: 34 AF XY: 0.589 AC XY: 43843 AN XY: 74386

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.586

Alfa AF: 0.563 Hom.: 15667

Bravo AF: 0.580

Asia WGS AF: 0.555 AC: 1932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.68
Dann	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3748492; hg19: chr20-17993269;