rs1206767

Positions:

• chr20-46959708-C-G

Variant summary

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

The NM_005244.5(EYA2):​c.-10-30293C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 152,326 control chromosomes in the GnomAD database, including 69,897 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 0.96 (69897 hom., cov: 33)
• Consequence: EYA2 NM_005244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYA2	NM_005244.5	c.-10-30293C>G		intron_variant		ENST00000327619.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA2	ENST00000327619.10	c.-10-30293C>G		intron_variant		2	NM_005244.5	P1
EYA2	ENST00000357410.7	c.-10-30293C>G		intron_variant		1
EYA2	ENST00000497062.6	c.-10-30293C>G		intron_variant		1
EYA2	ENST00000611592.4	c.-10-30293C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.955 AC: 145426 AN: 152208 Hom.: 69837 Cov.: 33

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.962

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.951

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

GnomAD4 genome AF: 0.955 AC: 145544 AN: 152326 Hom.: 69897 Cov.: 33 AF XY: 0.952 AC XY: 70933 AN XY: 74474

Gnomad4 AFR AF: 0.970

Gnomad4 AMR AF: 0.975

Gnomad4 ASJ AF: 0.980

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.962

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.947

Alfa AF: 0.958 Hom.: 3791

Bravo AF: 0.957

Asia WGS AF: 0.769 AC: 2675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.95
DANN	Benign	0.50

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: rs1206767; hg19: chr20-45588347;