chr17-12996646-T-C

Position:

• chr17-12996646-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.1560A>G​(p.Thr520Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,613,436 control chromosomes in the GnomAD database, including 69,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5692 hom., cov: 32)
  • Exomes 𝑓: 0.29 (63634 hom.)
• Consequence: ELAC2 NM_018127.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.71

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 17-12996646-T-C is Benign according to our data. Variant chr17-12996646-T-C is described in ClinVar as [Benign]. Clinvar id is 379971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAC2	NM_018127.7	c.1560A>G	p.Thr520Thr	synonymous_variant	17/24	ENST00000338034.9	NP_060597.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9	c.1560A>G	p.Thr520Thr	synonymous_variant	17/24	1	NM_018127.7	ENSP00000337445.4

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40637 AN: 151840 Hom.: 5682 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.0301

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.275

GnomAD3 exomes AF: 0.272 AC: 68113 AN: 250592 Hom.: 10006 AF XY: 0.276 AC XY: 37327 AN XY: 135484

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.254

Gnomad ASJ exome AF: 0.367

Gnomad EAS exome AF: 0.0342

Gnomad SAS exome AF: 0.278

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.308

GnomAD4 exome AF: 0.290 AC: 423972 AN: 1461478 Hom.: 63634 Cov.: 47 AF XY: 0.291 AC XY: 211294 AN XY: 727024

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.372

Gnomad4 EAS exome AF: 0.0311

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.268 AC: 40663 AN: 151958 Hom.: 5692 Cov.: 32 AF XY: 0.266 AC XY: 19738 AN XY: 74258

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.0300

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.272

Alfa AF: 0.264 Hom.: 1767

Bravo AF: 0.260

Asia WGS AF: 0.141 AC: 494 AN: 3478

EpiCase AF: 0.303

EpiControl AF: 0.298

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

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 15, 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 02, 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	-0.68
CADD	Benign	0.12
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs11545302; hg19: chr17-12899963; COSMIC: COSV62032597; COSMIC: COSV62032597;