rs6094514

chr20-46935081-C-T

Variant summary

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

The NM_005244.5(EYA2):c.-11+40094C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,176 control chromosomes in the GnomAD database, including 1,552 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 0.13 (1552 hom., cov: 32)
• Consequence: EYA2 NM_005244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288

Genes affected

EYA2 (HGNC:3520): (EYA transcriptional coactivator and phosphatase 2) This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may be post-translationally modified and may play a role in eye development. A similar protein in mice can act as a transcriptional activator. Alternative splicing results in multiple transcript variants, but the full-length natures of all of these variants have not yet been determined. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYA2	NM_005244.5	c.-11+40094C>T		intron_variant		ENST00000327619.10
EYA2	NM_172110.4	c.-11+40094C>T		intron_variant
EYA2	XM_005260327.3	c.-11+40094C>T		intron_variant
EYA2	XM_017027721.3	c.-11+40094C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA2	ENST00000327619.10	c.-11+40094C>T		intron_variant		2	NM_005244.5	P1
EYA2	ENST00000357410.7	c.-11+40094C>T		intron_variant		1
EYA2	ENST00000497062.6	c.-11+40094C>T		intron_variant		1
EYA2	ENST00000611592.4	c.-11+40094C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19691 AN: 152058 Hom.: 1550 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0667

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.130 AC: 19708 AN: 152176 Hom.: 1552 Cov.: 32 AF XY: 0.129 AC XY: 9624 AN XY: 74394

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0667

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.165

Alfa AF: 0.120 Hom.: 425

Bravo AF: 0.139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.76
Dann	Benign	0.82

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: rs6094514; hg19: chr20-45563720;