chr20-46935601-T-G

Variant names:

• chr20-46935601-T-G
• rs6094515
• NM_005244.5:c.-11+40614T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005244.5(EYA2):​c.-11+40614T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,994 control chromosomes in the GnomAD database, including 4,057 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 0.20 (4057 hom., cov: 32)
• Consequence: EYA2 NM_005244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005244.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA2	NM_005244.5	MANE Select	c.-11+40614T>G		intron	N/A	NP_005235.3
	EYA2	NM_172110.4		c.-11+40614T>G		intron	N/A	NP_742108.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA2	ENST00000327619.10	TSL:2 MANE Select	c.-11+40614T>G		intron	N/A	ENSP00000333640.5
	EYA2	ENST00000357410.7	TSL:1	c.-11+40614T>G		intron	N/A	ENSP00000349986.3
	EYA2	ENST00000611592.4	TSL:5	c.-11+40614T>G		intron	N/A	ENSP00000483392.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30053 AN: 151878 Hom.: 4037 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0683

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.198 AC: 30114 AN: 151994 Hom.: 4057 Cov.: 32 AF XY: 0.196 AC XY: 14598 AN XY: 74320

African (AFR) AF: 0.365 AC: 15110 AN: 41366

American (AMR) AF: 0.154 AC: 2358 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2145 AN: 5156

South Asian (SAS) AF: 0.136 AC: 654 AN: 4814

European-Finnish (FIN) AF: 0.0683 AC: 724 AN: 10602

Middle Eastern (MID) AF: 0.197 AC: 57 AN: 290

European-Non Finnish (NFE) AF: 0.117 AC: 7955 AN: 67988

Other (OTH) AF: 0.218 AC: 460 AN: 2112

Alfa AF: 0.166 Hom.: 360

Bravo AF: 0.215

Asia WGS AF: 0.283 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.0
DANN	Benign	0.74
PhyloP100		0.33
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: rs6094515; hg19: chr20-45564240;