20-46959708-C-G

Variant names:

• chr20-46959708-C-G
• rs1206767
• NM_005244.5:c.-10-30293C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005244.5(EYA2):​c.-10-30293C>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
• 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=-0.9).
• 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 rank	MANE	Protein	UniProt
EYA2	NM_005244.5	c.-10-30293C>G		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.-10-30293C>G		intron_variant	Intron 1 of 15	2	NM_005244.5	ENSP00000333640.5
EYA2	ENST00000357410.7	c.-10-30293C>G		intron_variant	Intron 1 of 13	1		ENSP00000349986.3
EYA2	ENST00000611592.4	c.-10-30293C>G		intron_variant	Intron 1 of 14	5		ENSP00000483392.1

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

African (AFR) AF: 0.970 AC: 40316 AN: 41572

American (AMR) AF: 0.975 AC: 14919 AN: 15308

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

East Asian (EAS) AF: 0.615 AC: 3173 AN: 5156

South Asian (SAS) AF: 0.888 AC: 4291 AN: 4830

European-Finnish (FIN) AF: 0.962 AC: 10213 AN: 10620

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

European-Non Finnish (NFE) AF: 0.971 AC: 66046 AN: 68046

Other (OTH) AF: 0.947 AC: 2003 AN: 2116

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
PhyloP100		-0.71
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: rs1206767; hg19: chr20-45588347;