20-47001428-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005244.5(EYA2):c.110G>A(p.Gly37Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000143 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
EYA2
NM_005244.5 missense, splice_region
NM_005244.5 missense, splice_region
Scores
13
6
Splicing: ADA: 0.9266
2
Clinical Significance
Conservation
PhyloP100: 4.47
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EYA2 | NM_005244.5 | c.110G>A | p.Gly37Asp | missense_variant, splice_region_variant | 3/16 | ENST00000327619.10 | NP_005235.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EYA2 | ENST00000327619.10 | c.110G>A | p.Gly37Asp | missense_variant, splice_region_variant | 3/16 | 2 | NM_005244.5 | ENSP00000333640.5 | ||
EYA2 | ENST00000497062.6 | c.110G>A | p.Gly37Asp | missense_variant, splice_region_variant | 3/16 | 1 | ENSP00000417105.3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152118Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251432Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135888
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461816Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727222
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74304
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 08, 2024 | The c.110G>A (p.G37D) alteration is located in exon 3 (coding exon 2) of the EYA2 gene. This alteration results from a G to A substitution at nucleotide position 110, causing the glycine (G) at amino acid position 37 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;.
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;.;M;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;.;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;D;D;.;D
Vest4
MutPred
Gain of disorder (P = 0.048);Gain of disorder (P = 0.048);Gain of disorder (P = 0.048);Gain of disorder (P = 0.048);Gain of disorder (P = 0.048);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at