NM_021220.4:c.327C>A

Variant names:

• chr20-18041718-G-T
• rs6111803
• NM_021220.4:c.327C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_021220.4(OVOL2):​c.327C>A​(p.Thr109Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 1,610,476 control chromosomes in the GnomAD database, including 3,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.057 (286 hom., cov: 31)
  • Exomes 𝑓: 0.065 (3530 hom.)
• Consequence: OVOL2 NM_021220.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.157
• Publications: 9 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, Labcorp Genetics (formerly Invitae), G2P
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 20-18041718-G-T is Benign according to our data. Variant chr20-18041718-G-T is described in ClinVar as Benign. ClinVar VariationId is 2037537.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.157 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0708 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021220.4. 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
	OVOL2	NM_021220.4	MANE Select	c.327C>A	p.Thr109Thr	synonymous	Exon 3 of 4	NP_067043.2
	OVOL2	NM_001303461.1		c.-70C>A		5_prime_UTR	Exon 3 of 4	NP_001290390.1	Q9BRP0-2
	OVOL2	NM_001303462.1		c.-70C>A		5_prime_UTR	Exon 2 of 3	NP_001290391.1	Q9BRP0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OVOL2	ENST00000278780.7	TSL:1 MANE Select	c.327C>A	p.Thr109Thr	synonymous	Exon 3 of 4	ENSP00000278780.5	Q9BRP0-1
	OVOL2	ENST00000462208.1	TSL:3	n.105C>A		non_coding_transcript_exon	Exon 2 of 2
	OVOL2	ENST00000483661.5	TSL:2	n.388C>A		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8654 AN: 151878 Hom.: 286 Cov.: 31

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0289

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.0353

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0465

GnomAD2 exomes AF: 0.0435 AC: 10855 AN: 249776 AF XY: 0.0439

Gnomad AFR exome AF: 0.0707

Gnomad AMR exome AF: 0.0191

Gnomad ASJ exome AF: 0.0242

Gnomad EAS exome AF: 0.00294

Gnomad FIN exome AF: 0.0242

Gnomad NFE exome AF: 0.0622

Gnomad OTH exome AF: 0.0393

GnomAD4 exome AF: 0.0647 AC: 94396 AN: 1458480 Hom.: 3530 Cov.: 34 AF XY: 0.0633 AC XY: 45879 AN XY: 725028

African (AFR) AF: 0.0699 AC: 2336 AN: 33408

American (AMR) AF: 0.0212 AC: 945 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 685 AN: 26100

East Asian (EAS) AF: 0.00187 AC: 74 AN: 39602

South Asian (SAS) AF: 0.0336 AC: 2892 AN: 86172

European-Finnish (FIN) AF: 0.0254 AC: 1352 AN: 53332

Middle Eastern (MID) AF: 0.0247 AC: 129 AN: 5232

European-Non Finnish (NFE) AF: 0.0741 AC: 82232 AN: 1109784

Other (OTH) AF: 0.0623 AC: 3751 AN: 60182

GnomAD4 genome AF: 0.0570 AC: 8664 AN: 151996 Hom.: 286 Cov.: 31 AF XY: 0.0537 AC XY: 3993 AN XY: 74314

African (AFR) AF: 0.0730 AC: 3024 AN: 41416

American (AMR) AF: 0.0288 AC: 440 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 73 AN: 3470

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5172

South Asian (SAS) AF: 0.0355 AC: 170 AN: 4782

European-Finnish (FIN) AF: 0.0240 AC: 255 AN: 10606

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0671 AC: 4563 AN: 67982

Other (OTH) AF: 0.0460 AC: 97 AN: 2110

Alfa AF: 0.0607 Hom.: 585

Bravo AF: 0.0581

Asia WGS AF: 0.0290 AC: 101 AN: 3478

EpiCase AF: 0.0629

EpiControl AF: 0.0580

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.6
DANN	Benign	0.62
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs6111803; hg19: chr20-18022362;