rs878131

chr20-47051863-A-G

Variant summary

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

The NM_005244.5(EYA2):c.416-20322A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,108 control chromosomes in the GnomAD database, including 39,428 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 0.72 (39428 hom., cov: 32)
• Consequence: EYA2 NM_005244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYA2	NM_005244.5	c.416-20322A>G		intron_variant		ENST00000327619.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA2	ENST00000327619.10	c.416-20322A>G		intron_variant		2	NM_005244.5	P1

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109138 AN: 151990 Hom.: 39383 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.718 AC: 109250 AN: 152108 Hom.: 39428 Cov.: 32 AF XY: 0.718 AC XY: 53366 AN XY: 74346

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.687

Alfa AF: 0.718 Hom.: 6662

Bravo AF: 0.708

Asia WGS AF: 0.665 AC: 2315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	3.8
Dann	Benign	0.33

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: rs878131; hg19: chr20-45680502;