20-18057908-A-G

Variant names:

• chr20-18057908-A-G
• rs869320630
• NM_021220.4:c.-274T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021220.4(OVOL2):​c.-274T>C variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.000000872 in 1,146,924 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: OVOL2 NM_021220.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82
• Publications: 0 publications found

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]

OVOL2 Gene-Disease associations (from GenCC):

• posterior polymorphous corneal dystrophy 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OVOL2	NM_021220.4	c.-274T>C		5_prime_UTR_variant	Exon 1 of 4	ENST00000278780.7	NP_067043.2
OVOL2	NM_001303461.1	c.-297+982T>C		intron_variant	Intron 1 of 3		NP_001290390.1
OVOL2	NM_001303462.1	c.-76+1172T>C		intron_variant	Intron 1 of 2		NP_001290391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OVOL2	ENST00000278780.7	c.-274T>C		5_prime_UTR_variant	Exon 1 of 4	1	NM_021220.4	ENSP00000278780.5
OVOL2	ENST00000483661.5	n.161+982T>C		intron_variant	Intron 1 of 3	2
OVOL2	ENST00000486776.5	n.109+1172T>C		intron_variant	Intron 1 of 3	3
OVOL2	ENST00000494030.1	n.109+1172T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.72e-7 AC: 1 AN: 1146924 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 548648

African (AFR) AF: 0.00 AC: 0 AN: 22410

American (AMR) AF: 0.00 AC: 0 AN: 8958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15216

East Asian (EAS) AF: 0.00 AC: 0 AN: 23630

South Asian (SAS) AF: 0.00 AC: 0 AN: 43330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3116

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 958458

Other (OTH) AF: 0.00 AC: 0 AN: 46646

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.90
PhyloP100		5.8
PromoterAI		-0.16	Neutral

Splicing

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

Other links and lift over

dbSNP: rs869320630; hg19: chr20-18038552;