12-6918025-G-A

Variant names:

• chr12-6918025-G-A
• NM_001975.3:c.530G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001975.3(ENO2):​c.530G>A​(p.Ser177Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ENO2 NM_001975.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23436221).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENO2	NM_001975.3	c.530G>A	p.Ser177Asn	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.530G>A	p.Ser177Asn	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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.530G>A (p.S177N) alteration is located in exon 7 (coding exon 6) of the ENO2 gene. This alteration results from a G to A substitution at nucleotide position 530, causing the serine (S) at amino acid position 177 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;T;.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	.;T;T;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;.;L
PhyloP100		1.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.080
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.31	T;T;T;T
Polyphen		0.0	B;B;.;B
Vest4		0.17
MutPred		0.53		Loss of phosphorylation at S177 (P = 0.0681);Loss of phosphorylation at S177 (P = 0.0681);.;Loss of phosphorylation at S177 (P = 0.0681);
MVP		0.45
MPC		0.53
ClinPred		0.50	T
GERP RS		4.8
Varity_R		0.57
gMVP		0.92
Mutation Taster		=40/60	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

hg19: chr12-7027189;