12-6919887-C-T

Variant names:

• chr12-6919887-C-T
• rs3213433
• NM_001975.3:c.865+124C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001975.3(ENO2):​c.865+124C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000109 in 914,382 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: ENO2 NM_001975.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• 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_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001975.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO2	NM_001975.3	MANE Select	c.865+124C>T		intron	N/A	NP_001966.1	Q6FHV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENO2	ENST00000229277.6	TSL:1 MANE Select	c.865+124C>T		intron	N/A	ENSP00000229277.1	P09104-1
	ENO2	ENST00000535366.5	TSL:1	c.865+124C>T		intron	N/A	ENSP00000437402.1	P09104-1
	ENO2	ENST00000541477.5	TSL:2	c.865+124C>T		intron	N/A	ENSP00000438873.1	P09104-1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000109 AC: 1 AN: 914382 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 458870

African (AFR) AF: 0.0000463 AC: 1 AN: 21596

American (AMR) AF: 0.00 AC: 0 AN: 26002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18022

East Asian (EAS) AF: 0.00 AC: 0 AN: 33494

South Asian (SAS) AF: 0.00 AC: 0 AN: 59324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2910

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 675248

Other (OTH) AF: 0.00 AC: 0 AN: 41558

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.66
PhyloP100		-0.019

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: rs3213433; hg19: chr12-7029051;