rs3213433

Positions:

• chr12-6919887-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001975.3(ENO2):​c.865+124C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 1,066,340 control chromosomes in the GnomAD database, including 1,871 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.051 (574 hom., cov: 30)
  • Exomes 𝑓: 0.016 (1297 hom.)
• Consequence: ENO2 NM_001975.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENO2	NM_001975.3	c.865+124C>A		intron_variant		ENST00000229277.6	NP_001966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENO2	ENST00000229277.6	c.865+124C>A		intron_variant		1	NM_001975.3	ENSP00000229277	P1

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7715 AN: 151892 Hom.: 569 Cov.: 30

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0271

Gnomad ASJ AF: 0.00693

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.0485

GnomAD4 exome AF: 0.0161 AC: 14684 AN: 914330 Hom.: 1297 AF XY: 0.0153 AC XY: 7000 AN XY: 458844

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.0164

Gnomad4 ASJ exome AF: 0.00860

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.0108

Gnomad4 FIN exome AF: 0.000138

Gnomad4 NFE exome AF: 0.00178

Gnomad4 OTH exome AF: 0.0258

GnomAD4 genome AF: 0.0509 AC: 7732 AN: 152010 Hom.: 574 Cov.: 30 AF XY: 0.0505 AC XY: 3754 AN XY: 74288

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0269

Gnomad4 ASJ AF: 0.00693

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00210

Gnomad4 OTH AF: 0.0490

Alfa AF: 0.0190 Hom.: 52

Bravo AF: 0.0587

Asia WGS AF: 0.0810 AC: 283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.6
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs3213433; hg19: chr12-7029051;