rs2302069

Variant names:

• chr17-13010707-T-C
• rs2302069
• NM_018127.7:c.680-36A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.35
• Publications: 9 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 -20 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 VariationId is 1246967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ELAC2	NM_018127.7	c.680-36A>G		intron_variant	Intron 7 of 23	ENST00000338034.9	NP_060597.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9	c.680-36A>G		intron_variant	Intron 7 of 23	1	NM_018127.7	ENSP00000337445.4
ELAC2	ENST00000446899.5	c.8-36A>G		intron_variant	Intron 1 of 9	5		ENSP00000406192.1

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

GnomAD2 exomes AF: 0.126 AC: 31498 AN: 249866 AF XY: 0.127

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 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

African (AFR) AF: 0.0198 AC: 652 AN: 32978

American (AMR) AF: 0.155 AC: 6903 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2890 AN: 25992

East Asian (EAS) AF: 0.0272 AC: 1075 AN: 39548

South Asian (SAS) AF: 0.127 AC: 10877 AN: 85792

European-Finnish (FIN) AF: 0.187 AC: 9919 AN: 53120

Middle Eastern (MID) AF: 0.0708 AC: 406 AN: 5732

European-Non Finnish (NFE) AF: 0.138 AC: 150408 AN: 1091790

Other (OTH) AF: 0.119 AC: 7109 AN: 59676

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

African (AFR) AF: 0.0255 AC: 1060 AN: 41554

American (AMR) AF: 0.128 AC: 1952 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 397 AN: 3466

East Asian (EAS) AF: 0.0236 AC: 122 AN: 5180

South Asian (SAS) AF: 0.130 AC: 629 AN: 4824

European-Finnish (FIN) AF: 0.185 AC: 1958 AN: 10580

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9288 AN: 68016

Other (OTH) AF: 0.0926 AC: 196 AN: 2116

Alfa AF: 0.126 Hom.: 849

Bravo AF: 0.0930

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.11
DANN	Benign	0.62
PhyloP100		-2.4
Mutation Taster		=100/0	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: rs2302069; hg19: chr17-12914024; COSMIC: COSV62032153; COSMIC: COSV62032153;