rs17552022

Positions:

• chr17-12994978-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018127.7(ELAC2):​c.1893A>G​(p.Thr631=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,614,118 control chromosomes in the GnomAD database, including 11,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (797 hom., cov: 33)
  • Exomes 𝑓: 0.12 (10762 hom.)
• Consequence: ELAC2 NM_018127.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.55

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=-0.88).
• BP6: Variant 17-12994978-T-C is Benign according to our data. Variant chr17-12994978-T-C is described in ClinVar as [Benign]. Clinvar id is 380022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.55 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAC2	NM_018127.7	c.1893A>G	p.Thr631=	synonymous_variant	20/24	ENST00000338034.9	NP_060597.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9	c.1893A>G	p.Thr631=	synonymous_variant	20/24	1	NM_018127.7	ENSP00000337445	P2

Frequencies

GnomAD3 genomes AF: 0.0866 AC: 13173 AN: 152160 Hom.: 796 Cov.: 33

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0975

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.110

GnomAD3 exomes AF: 0.0987 AC: 24819 AN: 251480 Hom.: 1606 AF XY: 0.104 AC XY: 14135 AN XY: 135914

Gnomad AFR exome AF: 0.0204

Gnomad AMR exome AF: 0.0593

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.000544

Gnomad SAS exome AF: 0.112

Gnomad FIN exome AF: 0.0797

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.116 AC: 169034 AN: 1461840 Hom.: 10762 Cov.: 34 AF XY: 0.117 AC XY: 85164 AN XY: 727226

Gnomad4 AFR exome AF: 0.0218

Gnomad4 AMR exome AF: 0.0623

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.000453

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.0823

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.0865 AC: 13169 AN: 152278 Hom.: 797 Cov.: 33 AF XY: 0.0846 AC XY: 6300 AN XY: 74450

Gnomad4 AFR AF: 0.0215

Gnomad4 AMR AF: 0.0764

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0976

Gnomad4 FIN AF: 0.0824

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.109

Alfa AF: 0.122 Hom.: 1588

Bravo AF: 0.0843

Asia WGS AF: 0.0390 AC: 138 AN: 3478

EpiCase AF: 0.134

EpiControl AF: 0.140

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Combined oxidative phosphorylation defect type 17 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 25, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 16, 2015

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. -

Prostate cancer, hereditary, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.095
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17552022; hg19: chr17-12898295; COSMIC: COSV52401329; COSMIC: COSV52401329;