Variant 20-47005063-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005244.5(EYA2):c.277G>A(p.Ala93Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000996 in 1,613,784 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00054 ( 5 hom. )

Consequence

EYA2
NM_005244.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.65

Variant links:

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]

EYA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00952062).

BP6

Variant 20-47005063-G-A is Benign according to our data. Variant chr20-47005063-G-A is described in ClinVar as [Benign]. Clinvar id is 781566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00539 (820/152248) while in subpopulation AFR AF= 0.0188 (781/41538). AF 95% confidence interval is 0.0177. There are 4 homozygotes in gnomad4. There are 392 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYA2	NM_005244.5 linkuse as main transcript	c.277G>A	p.Ala93Thr	missense_variant	4/16	ENST00000327619.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA2	ENST00000327619.10 linkuse as main transcript	c.277G>A	p.Ala93Thr	missense_variant	4/16	2	NM_005244.5	P1	O00167-1

Frequencies

GnomAD3 genomes

AF:

0.00539

AC:

820

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0189

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00142

AC:

355

AN:

249722

Hom.:

AF XY:

0.000977

AC XY:

132

AN XY:

135110

show subpopulations

Gnomad AFR exome

AF:

0.0195

Gnomad AMR exome

AF:

0.000724

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000538

AC:

787

AN:

1461536

Hom.:

Cov.:

AF XY:

0.000462

AC XY:

336

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.0195

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00539

AC:

820

AN:

152248

Hom.:

Cov.:

AF XY:

0.00527

AC XY:

392

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0188

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00621

ESP6500AA

AF:

0.0200

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00175

AC:

213

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;.;T;.;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.071

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.83

T;T;T;T;.;T

MetaRNN

Benign

0.0095

T;T;T;T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

0.85

L;L;.;L;.;.

MutationTaster

Benign

0.84

D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.20

N;N;.;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.78

T;T;.;T;T;T

Sift4G

Benign

0.72

T;T;T;T;T;T

Polyphen

0.0

B;B;B;.;B;.

Vest4

0.15

MVP

0.79

MPC

0.11

ClinPred

0.015

GERP RS

4.6

Varity_R

0.034

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over