17-12994978-T-C

Variant names:

• chr17-12994978-T-C
• rs17552022
• NM_018127.7:c.1893A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018127.7(ELAC2):​c.1893A>G​(p.Thr631Thr) 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
• Publications: 16 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.88).
• BP6: Variant 17-12994978-T-C is Benign according to our data. Variant chr17-12994978-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC2	NM_018127.7	MANE Select	c.1893A>G	p.Thr631Thr	synonymous	Exon 20 of 24	NP_060597.4
	ELAC2	NM_173717.2		c.1890A>G	p.Thr630Thr	synonymous	Exon 20 of 24	NP_776065.1
	ELAC2	NM_001165962.2		c.1773A>G	p.Thr591Thr	synonymous	Exon 19 of 23	NP_001159434.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC2	ENST00000338034.9	TSL:1 MANE Select	c.1893A>G	p.Thr631Thr	synonymous	Exon 20 of 24	ENSP00000337445.4
	ELAC2	ENST00000395962.6	TSL:2	c.1836A>G	p.Thr612Thr	synonymous	Exon 20 of 24	ENSP00000379291.1
	ELAC2	ENST00000426905.7	TSL:2	c.1773A>G	p.Thr591Thr	synonymous	Exon 19 of 23	ENSP00000405223.3

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

GnomAD2 exomes AF: 0.0987 AC: 24819 AN: 251480 AF XY: 0.104

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 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

African (AFR) AF: 0.0218 AC: 729 AN: 33480

American (AMR) AF: 0.0623 AC: 2788 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 4974 AN: 26136

East Asian (EAS) AF: 0.000453 AC: 18 AN: 39700

South Asian (SAS) AF: 0.117 AC: 10110 AN: 86258

European-Finnish (FIN) AF: 0.0823 AC: 4396 AN: 53384

Middle Eastern (MID) AF: 0.205 AC: 1183 AN: 5768

European-Non Finnish (NFE) AF: 0.124 AC: 137746 AN: 1111994

Other (OTH) AF: 0.117 AC: 7090 AN: 60396

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

African (AFR) AF: 0.0215 AC: 896 AN: 41580

American (AMR) AF: 0.0764 AC: 1169 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0976 AC: 471 AN: 4826

European-Finnish (FIN) AF: 0.0824 AC: 874 AN: 10612

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8546 AN: 68000

Other (OTH) AF: 0.109 AC: 229 AN: 2104

Alfa AF: 0.117 Hom.: 1877

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

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 25, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not specified Benign:1

Dec 16, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.095
DANN	Benign	0.49
PhyloP100		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

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