17-12992957-C-G

Variant names:

• chr17-12992957-C-G
• NM_018127.7:c.2342G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018127.7(ELAC2):​c.2342G>C​(p.Arg781Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ELAC2 NM_018127.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.52

Genes affected

ELAC2 (HGNC:14198): (elaC ribonuclease Z 2) The protein encoded by this gene has a C-terminal domain with tRNA 3′ processing endoribonuclease activity, which catalyzes the removal of the 3' trailer from precursor tRNAs. The protein also interacts with activated Smad family member 2 (Smad2) and its nuclear partner forkhead box H1 (also known as FAST-1), and reduced expression can suppress transforming growth factor-beta induced growth arrest. Mutations in this gene result in an increased risk of prostate cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELAC2	NM_018127.7	c.2342G>C	p.Arg781Pro	missense_variant	Exon 24 of 24	ENST00000338034.9	NP_060597.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9	c.2342G>C	p.Arg781Pro	missense_variant	Exon 24 of 24	1	NM_018127.7	ENSP00000337445.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725942

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	30
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T;.;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Uncertain	-0.011	T
MutationAssessor	Pathogenic	3.0	M;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-4.7	D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.74
MutPred		0.56		Gain of loop (P = 0.002);.;.;
MVP		0.90
MPC		0.90
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.89
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-12896274;