17-12992667-G-C

Variant names:

• chr17-12992667-G-C
• rs1044564
• NM_018127.7:c.*151C>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.*151C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 895,568 control chromosomes in the GnomAD database, including 159,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24443 hom., cov: 32)
  • Exomes 𝑓: 0.60 (135369 hom.)
• Consequence: ELAC2 NM_018127.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.553
• Publications: 20 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=-0.85).
• BP6: Variant 17-12992667-G-C is Benign according to our data. Variant chr17-12992667-G-C is described in ClinVar as [Benign]. Clinvar id is 1239530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELAC2	NM_018127.7	c.*151C>G		3_prime_UTR_variant	Exon 24 of 24	ENST00000338034.9	NP_060597.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9	c.*151C>G		3_prime_UTR_variant	Exon 24 of 24	1	NM_018127.7	ENSP00000337445.4

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85553 AN: 151736 Hom.: 24427 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.551

GnomAD4 exome AF: 0.601 AC: 446687 AN: 743712 Hom.: 135369 Cov.: 10 AF XY: 0.598 AC XY: 227818 AN XY: 380704

African (AFR) AF: 0.454 AC: 8659 AN: 19060

American (AMR) AF: 0.592 AC: 17901 AN: 30250

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 8901 AN: 17704

East Asian (EAS) AF: 0.464 AC: 15122 AN: 32574

South Asian (SAS) AF: 0.544 AC: 31760 AN: 58384

European-Finnish (FIN) AF: 0.612 AC: 20376 AN: 33270

Middle Eastern (MID) AF: 0.517 AC: 1376 AN: 2662

European-Non Finnish (NFE) AF: 0.626 AC: 321444 AN: 513816

Other (OTH) AF: 0.588 AC: 21148 AN: 35992

GnomAD4 genome AF: 0.564 AC: 85613 AN: 151856 Hom.: 24443 Cov.: 32 AF XY: 0.564 AC XY: 41832 AN XY: 74182

African (AFR) AF: 0.459 AC: 18990 AN: 41406

American (AMR) AF: 0.584 AC: 8907 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1728 AN: 3468

East Asian (EAS) AF: 0.511 AC: 2616 AN: 5120

South Asian (SAS) AF: 0.562 AC: 2707 AN: 4816

European-Finnish (FIN) AF: 0.608 AC: 6395 AN: 10526

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.625 AC: 42465 AN: 67946

Other (OTH) AF: 0.551 AC: 1162 AN: 2108

Alfa AF: 0.592 Hom.: 3340

Bravo AF: 0.557

Asia WGS AF: 0.584 AC: 2032 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	-0.85
CADD	Benign	4.1
DANN	Benign	0.53
PhyloP100		0.55
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: rs1044564; hg19: chr17-12895984; COSMIC: COSV52391928; COSMIC: COSV52391928;