rs1206765

chr20-46958080-G-Achr20-46958080-G-Cchr20-46958080-G-T

Variant summary

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

The NM_005244.5(EYA2):c.-10-31921G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 152,244 control chromosomes in the GnomAD database, including 69,471 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 0.95 (69471 hom., cov: 31)
• Consequence: EYA2 NM_005244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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=-0.95).
• 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.-10-31921G>A		intron_variant		ENST00000327619.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA2	ENST00000327619.10	c.-10-31921G>A		intron_variant		2	NM_005244.5	P1
EYA2	ENST00000357410.7	c.-10-31921G>A		intron_variant		1
EYA2	ENST00000497062.6	c.-10-31921G>A		intron_variant		1
EYA2	ENST00000611592.4	c.-10-31921G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.953 AC: 144926 AN: 152126 Hom.: 69412 Cov.: 31

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.962

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.949

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

GnomAD4 genome AF: 0.953 AC: 145043 AN: 152244 Hom.: 69471 Cov.: 31 AF XY: 0.950 AC XY: 70709 AN XY: 74452

Gnomad4 AFR AF: 0.962

Gnomad4 AMR AF: 0.974

Gnomad4 ASJ AF: 0.980

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.962

Gnomad4 NFE AF: 0.970

Gnomad4 OTH AF: 0.943

Alfa AF: 0.959 Hom.: 5818

Bravo AF: 0.954

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.1
Dann	Benign	0.73

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: rs1206765; hg19: chr20-45586719;