rs2302069

chr17-13010707-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018127.7(ELAC2):c.680-36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,591,530 control chromosomes in the GnomAD database, including 14,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1050 hom., cov: 33)
  • Exomes 𝑓: 0.13 (13293 hom.)
• Consequence: ELAC2 NM_018127.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.35

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-13010707-T-C is Benign according to our data. Variant chr17-13010707-T-C is described in ClinVar as [Benign]. Clinvar id is 1246967.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELAC2	NM_018127.7	c.680-36A>G		intron_variant		ENST00000338034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELAC2	ENST00000338034.9	c.680-36A>G		intron_variant		1	NM_018127.7	P2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15705 AN: 152124 Hom.: 1049 Cov.: 33

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.0941

GnomAD3 exomes AF: 0.126 AC: 31498 AN: 249866 Hom.: 2307 AF XY: 0.127 AC XY: 17205 AN XY: 135364

Gnomad AFR exome AF: 0.0217

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.0273

Gnomad SAS exome AF: 0.125

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.132 AC: 190239 AN: 1439288 Hom.: 13293 Cov.: 26 AF XY: 0.132 AC XY: 94476 AN XY: 717786

Gnomad4 AFR exome AF: 0.0198

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.0272

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.103 AC: 15702 AN: 152242 Hom.: 1050 Cov.: 33 AF XY: 0.106 AC XY: 7866 AN XY: 74430

Gnomad4 AFR AF: 0.0255

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0236

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.0926

Alfa AF: 0.126 Hom.: 787

Bravo AF: 0.0930

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.11
Dann	Benign	0.62

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: rs2302069; hg19: chr17-12914024; COSMIC: COSV62032153; COSMIC: COSV62032153;