20-46958080-G-A

Variant names:

• chr20-46958080-G-A
• rs1206765
• NM_005244.5:c.-10-31921G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.95).
• 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 rank	MANE	Protein	UniProt
EYA2	NM_005244.5	c.-10-31921G>A		intron_variant	Intron 1 of 15	ENST00000327619.10	NP_005235.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYA2	ENST00000327619.10	c.-10-31921G>A		intron_variant	Intron 1 of 15	2	NM_005244.5	ENSP00000333640.5
EYA2	ENST00000357410.7	c.-10-31921G>A		intron_variant	Intron 1 of 13	1		ENSP00000349986.3
EYA2	ENST00000611592.4	c.-10-31921G>A		intron_variant	Intron 1 of 14	5		ENSP00000483392.1

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

African (AFR) AF: 0.962 AC: 39962 AN: 41538

American (AMR) AF: 0.974 AC: 14895 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.980 AC: 3403 AN: 3472

East Asian (EAS) AF: 0.602 AC: 3099 AN: 5150

South Asian (SAS) AF: 0.888 AC: 4285 AN: 4826

European-Finnish (FIN) AF: 0.962 AC: 10202 AN: 10610

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.970 AC: 66025 AN: 68032

Other (OTH) AF: 0.943 AC: 1992 AN: 2112

Alfa AF: 0.960 Hom.: 6191

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
PhyloP100		-0.38
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: rs1206765; hg19: chr20-45586719;