chr12-6916498-G-C

Variant names:

• chr12-6916498-G-C
• rs542780041
• NM_001975.3:c.167G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001975.3(ENO2):​c.167G>C​(p.Arg56Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R56C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ENO2 NM_001975.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.03
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENO2	NM_001975.3	c.167G>C	p.Arg56Pro	missense_variant	Exon 3 of 12	ENST00000229277.6	NP_001966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENO2	ENST00000229277.6	c.167G>C	p.Arg56Pro	missense_variant	Exon 3 of 12	1	NM_001975.3	ENSP00000229277.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461822 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727204

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T;T;.;.;T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D;.;D;D;D;.
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Pathogenic	4.3	.;H;H;H;.;H
PhyloP100		8.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.4	D;N;N;N;N;N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0080	D;D;D;D;T;D
Sift4G	Uncertain	0.0040	D;D;D;D;D;D
Polyphen		0.95	.;P;P;.;.;P
Vest4		0.73, 0.73, 0.74, 0.75
MutPred		0.52		Loss of MoRF binding (P = 0.0251);Loss of MoRF binding (P = 0.0251);Loss of MoRF binding (P = 0.0251);Loss of MoRF binding (P = 0.0251);Loss of MoRF binding (P = 0.0251);Loss of MoRF binding (P = 0.0251);
MVP		0.78
MPC		1.8
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.95
gMVP		0.95
Mutation Taster		=25/75	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: rs542780041; hg19: chr12-7025662;