20-47024496-C-G

Variant names:

• chr20-47024496-C-G
• rs2145133
• NM_005244.5:c.415+8199C>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.415+8199C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,204 control chromosomes in the GnomAD database, including 52,346 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 0.81 (52346 hom., cov: 33)
• Consequence: EYA2 NM_005244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYA2	NM_005244.5	c.415+8199C>G		intron_variant	Intron 5 of 15	ENST00000327619.10	NP_005235.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYA2	ENST00000327619.10	c.415+8199C>G		intron_variant	Intron 5 of 15	2	NM_005244.5	ENSP00000333640.5

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122723 AN: 152086 Hom.: 52345 Cov.: 33

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.962

Gnomad OTH AF: 0.824

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

GnomAD4 genome AF: 0.806 AC: 122751 AN: 152204 Hom.: 52346 Cov.: 33 AF XY: 0.806 AC XY: 59961 AN XY: 74422

African (AFR) AF: 0.518 AC: 21501 AN: 41468

American (AMR) AF: 0.799 AC: 12214 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3145 AN: 3470

East Asian (EAS) AF: 0.647 AC: 3348 AN: 5172

South Asian (SAS) AF: 0.923 AC: 4461 AN: 4834

European-Finnish (FIN) AF: 0.918 AC: 9741 AN: 10612

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.962 AC: 65430 AN: 68032

Other (OTH) AF: 0.824 AC: 1741 AN: 2114

Alfa AF: 0.845 Hom.: 3102

Bravo AF: 0.782

Asia WGS AF: 0.747 AC: 2600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.62
PhyloP100		0.28
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: rs2145133; hg19: chr20-45653135;