12-6919954-C-T

Position:

• chr12-6919954-C-T

Variant summary

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

The NM_001975.3(ENO2):​c.865+191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,874 control chromosomes in the GnomAD database, including 7,281 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 0.31 (7281 hom., cov: 30)
• Consequence: ENO2 NM_001975.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENO2	NM_001975.3	c.865+191C>T		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+191C>T		intron_variant		1	NM_001975.3	ENSP00000229277.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46967 AN: 151756 Hom.: 7278 Cov.: 30

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.309 AC: 46977 AN: 151874 Hom.: 7281 Cov.: 30 AF XY: 0.306 AC XY: 22744 AN XY: 74248

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.333

Alfa AF: 0.305 Hom.: 845

Bravo AF: 0.309

Asia WGS AF: 0.309 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3213434; hg19: chr12-7029118;