NM_005244.5:c.451G>C

Variant names:

• chr20-47072220-G-C
• NM_005244.5:c.451G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005244.5(EYA2):​c.451G>C​(p.Gly151Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EYA2 NM_005244.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

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]

ENSG00000239783 (HGNC:56964):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22212258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYA2	NM_005244.5	c.451G>C	p.Gly151Arg	missense_variant	Exon 6 of 16	ENST00000327619.10	NP_005235.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYA2	ENST00000327619.10	c.451G>C	p.Gly151Arg	missense_variant	Exon 6 of 16	2	NM_005244.5	ENSP00000333640.5
EYA2	ENST00000497062.6	c.379G>C	p.Gly127Arg	missense_variant	Exon 6 of 16	1		ENSP00000417105.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460856 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726608

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	0.0061	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.63
DEOGEN2	Benign	0.060	T;.;T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Pathogenic	0.98	D;D;D;D;.
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.0	N;N;.;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.80	N;N;.;.;N
REVEL	Benign	0.26
Sift	Uncertain	0.0070	D;D;.;.;D
Sift4G	Benign	0.51	T;T;T;T;T
Polyphen		0.056	B;B;B;.;B
Vest4		0.36
MutPred		0.39		Gain of methylation at G151 (P = 0.0267);Gain of methylation at G151 (P = 0.0267);Gain of methylation at G151 (P = 0.0267);.;Gain of methylation at G151 (P = 0.0267);
MVP		0.57
MPC		0.16
ClinPred		0.17	T
GERP RS		-1.3
Varity_R		0.11
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-45700859;