20-47040810-T-G

Variant summary

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

The NM_005244.5(EYA2):c.415+24513T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 151,954 control chromosomes in the GnomAD database, including 1,977 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 0.16 (1977 hom., cov: 32)
• Consequence: EYA2 NM_005244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.723

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYA2	NM_005244.5	c.415+24513T>G		intron_variant		ENST00000327619.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA2	ENST00000327619.10	c.415+24513T>G		intron_variant		2	NM_005244.5	P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24231 AN: 151836 Hom.: 1978 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.160 AC: 24250 AN: 151954 Hom.: 1977 Cov.: 32 AF XY: 0.158 AC XY: 11729 AN XY: 74274

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.152

Alfa AF: 0.163 Hom.: 2869

Bravo AF: 0.155

Asia WGS AF: 0.125 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.7
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: rs4810599; hg19: chr20-45669449;