chr20-18012625-C-T

Variant names:

• chr20-18012625-C-T
• rs3748492

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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: PTMAP3 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 3 publications found

Genes affected

PTMAP3 (HGNC:9626): (prothymosin alpha pseudogene 3)

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]

OVOL2 Gene-Disease associations (from GenCC):

• posterior polymorphous corneal dystrophy 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital hereditary endothelial dystrophy type I

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• posterior polymorphous corneal dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000486776.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OVOL2	ENST00000486776.5	TSL:3	n.300-15873G>A		intron	N/A

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

African (AFR) AF: 0.673 AC: 27962 AN: 41520

American (AMR) AF: 0.519 AC: 7933 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2293 AN: 3472

East Asian (EAS) AF: 0.466 AC: 2414 AN: 5176

South Asian (SAS) AF: 0.600 AC: 2897 AN: 4832

European-Finnish (FIN) AF: 0.581 AC: 6140 AN: 10570

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.552 AC: 37555 AN: 67994

Other (OTH) AF: 0.586 AC: 1238 AN: 2112

Alfa AF: 0.566 Hom.: 19399

Bravo AF: 0.580

Asia WGS AF: 0.555 AC: 1932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.68
DANN	Benign	0.26
PhyloP100		2.2

Splicing

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

Other links and lift over

dbSNP: rs3748492; hg19: chr20-17993269;