rs117582762

Variant names:

• chr17-12995946-G-A
• rs117582762
• NM_018127.7:c.1692C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018127.7(ELAC2):​c.1692C>T​(p.Arg564Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000494 in 1,596,304 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00050 (9 hom.)
• Consequence: ELAC2 NM_018127.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.48
• Publications: 3 publications found

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]

ELAC2 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation defect type 17

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-12995946-G-A is Benign according to our data. Variant chr17-12995946-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 382473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.48 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000486 (74/152366) while in subpopulation EAS AF = 0.00251 (13/5184). AF 95% confidence interval is 0.00148. There are 0 homozygotes in GnomAd4. There are 43 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018127.7. 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
	ELAC2	NM_018127.7	MANE Select	c.1692C>T	p.Arg564Arg	synonymous	Exon 18 of 24	NP_060597.4
	ELAC2	NM_173717.2		c.1689C>T	p.Arg563Arg	synonymous	Exon 18 of 24	NP_776065.1
	ELAC2	NM_001165962.2		c.1572C>T	p.Arg524Arg	synonymous	Exon 17 of 23	NP_001159434.1	Q9BQ52-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC2	ENST00000338034.9	TSL:1 MANE Select	c.1692C>T	p.Arg564Arg	synonymous	Exon 18 of 24	ENSP00000337445.4	Q9BQ52-1
	ELAC2	ENST00000923774.1		c.1794C>T	p.Arg598Arg	synonymous	Exon 19 of 25	ENSP00000593833.1
	ELAC2	ENST00000860253.1		c.1716C>T	p.Arg572Arg	synonymous	Exon 19 of 25	ENSP00000530312.1

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 74 AN: 152248 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00136 AC: 302 AN: 221690 AF XY: 0.00102

Gnomad AFR exome AF: 0.000525

Gnomad AMR exome AF: 0.00708

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00293

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000821

Gnomad OTH exome AF: 0.000890

GnomAD4 exome AF: 0.000495 AC: 715 AN: 1443938 Hom.: 9 Cov.: 33 AF XY: 0.000468 AC XY: 335 AN XY: 716322

African (AFR) AF: 0.000211 AC: 7 AN: 33136

American (AMR) AF: 0.00612 AC: 262 AN: 42832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25776

East Asian (EAS) AF: 0.00914 AC: 358 AN: 39154

South Asian (SAS) AF: 0.0000479 AC: 4 AN: 83448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000526 AC: 58 AN: 1102014

Other (OTH) AF: 0.000435 AC: 26 AN: 59720

GnomAD4 genome AF: 0.000486 AC: 74 AN: 152366 Hom.: 0 Cov.: 33 AF XY: 0.000577 AC XY: 43 AN XY: 74508

African (AFR) AF: 0.000601 AC: 25 AN: 41598

American (AMR) AF: 0.00157 AC: 24 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000256 Hom.: 0

Bravo AF: 0.000612

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Combined oxidative phosphorylation defect type 17 (1)
-	-	1	ELAC2-related disorder (1)
-	-	1	not specified (1)
-	-	1	Prostate cancer, hereditary, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.62
DANN	Benign	0.94
PhyloP100		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=98/2	polymorphism

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: rs117582762; hg19: chr17-12899263; COSMIC: COSV61645094; COSMIC: COSV61645094;