12-6918097-G-T

Variant names:

• chr12-6918097-G-T
• rs1555141813
• NM_001975.3:c.602G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001975.3(ENO2):​c.602G>T​(p.Gly201Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G201S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ENO2 NM_001975.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

Genes affected

ENO2 (HGNC:3353): (enolase 2) This gene encodes one of the three enolase isoenzymes found in mammals. This isoenzyme, a homodimer, is found in mature neurons and cells of neuronal origin. A switch from alpha enolase to gamma enolase occurs in neural tissue during development in rats and primates. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENO2	NM_001975.3	c.602G>T	p.Gly201Val	missense_variant	Exon 7 of 12	ENST00000229277.6	NP_001966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENO2	ENST00000229277.6	c.602G>T	p.Gly201Val	missense_variant	Exon 7 of 12	1	NM_001975.3	ENSP00000229277.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;D;.;D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	.;D;D;.
M_CAP	Pathogenic	0.37	D
MetaRNN	Pathogenic	0.95	D;D;D;D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Pathogenic	5.0	H;H;.;H
PhyloP100		10
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-7.7	D;D;D;D
REVEL	Pathogenic	0.73
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		0.98	D;D;.;D
Vest4		0.87
MutPred		0.80		Loss of disorder (P = 0.0402);Loss of disorder (P = 0.0402);.;Loss of disorder (P = 0.0402);
MVP		0.94
MPC		1.7
ClinPred		1.0	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.99
gMVP		0.98
Mutation Taster		=32/68	disease causing

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: rs1555141813; hg19: chr12-7027261;