rs117582762

Positions:

• chr17-12995946-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018127.7(ELAC2):​c.1692C>T​(p.Arg564=) 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:3
• Conservation: PhyloP100: -2.48

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 Benign. Variant got -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAC2	NM_018127.7	c.1692C>T	p.Arg564=	synonymous_variant	18/24	ENST00000338034.9	NP_060597.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9	c.1692C>T	p.Arg564=	synonymous_variant	18/24	1	NM_018127.7	ENSP00000337445	P2

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

GnomAD3 exomes AF: 0.00136 AC: 302 AN: 221690 Hom.: 3 AF XY: 0.00102 AC XY: 121 AN XY: 119200

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 SAS exome AF: 0.000110

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

Gnomad4 AFR exome AF: 0.000211

Gnomad4 AMR exome AF: 0.00612

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00914

Gnomad4 SAS exome AF: 0.0000479

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000526

Gnomad4 OTH exome AF: 0.000435

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

Gnomad4 AFR AF: 0.000601

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000311 Hom.: 0

Bravo AF: 0.000612

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 17, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

ELAC2-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Combined oxidative phosphorylation defect type 17 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.62
DANN	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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