rs13041757

Positions:

• chr20-46971641-G-A
• chr20-46971641-G-C

Variant summary

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

The NM_005244.5(EYA2):​c.-10-18360G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,156 control chromosomes in the GnomAD database, including 10,546 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 0.34 (10546 hom., cov: 33)
• Consequence: EYA2 NM_005244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYA2	NM_005244.5	c.-10-18360G>A		intron_variant		ENST00000327619.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA2	ENST00000327619.10	c.-10-18360G>A		intron_variant		2	NM_005244.5	P1
EYA2	ENST00000357410.7	c.-10-18360G>A		intron_variant		1
EYA2	ENST00000497062.6	c.-10-18360G>A		intron_variant		1
EYA2	ENST00000611592.4	c.-10-18360G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52222 AN: 152038 Hom.: 10544 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.343 AC: 52220 AN: 152156 Hom.: 10546 Cov.: 33 AF XY: 0.340 AC XY: 25323 AN XY: 74398

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.356

Alfa AF: 0.414 Hom.: 13182

Bravo AF: 0.320

Asia WGS AF: 0.252 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.045
DANN	Benign	0.45

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: rs13041757; hg19: chr20-45600280;