17-12992498-C-T

Variant names:

• chr17-12992498-C-T
• rs2523
• NM_018127.7:c.*320G>A

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.*320G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 459,908 control chromosomes in the GnomAD database, including 79,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (24947 hom., cov: 32)
  • Exomes 𝑓: 0.59 (54695 hom.)
• Consequence: ELAC2 NM_018127.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.323
• Publications: 34 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=-0.84).
• BP6: Variant 17-12992498-C-T is Benign according to our data. Variant chr17-12992498-C-T is described in ClinVar as [Benign]. Clinvar id is 1177697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELAC2	NM_018127.7	c.*320G>A		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.*320G>A		3_prime_UTR_variant	Exon 24 of 24	1	NM_018127.7	ENSP00000337445.4

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86536 AN: 151790 Hom.: 24926 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.553

GnomAD4 exome AF: 0.592 AC: 182220 AN: 307998 Hom.: 54695 Cov.: 0 AF XY: 0.588 AC XY: 93503 AN XY: 158928

African (AFR) AF: 0.478 AC: 4952 AN: 10352

American (AMR) AF: 0.588 AC: 7479 AN: 12730

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 5428 AN: 10602

East Asian (EAS) AF: 0.462 AC: 9845 AN: 21290

South Asian (SAS) AF: 0.554 AC: 20470 AN: 36934

European-Finnish (FIN) AF: 0.610 AC: 8581 AN: 14076

Middle Eastern (MID) AF: 0.530 AC: 723 AN: 1364

European-Non Finnish (NFE) AF: 0.625 AC: 113889 AN: 182080

Other (OTH) AF: 0.584 AC: 10853 AN: 18570

GnomAD4 genome AF: 0.570 AC: 86598 AN: 151910 Hom.: 24947 Cov.: 32 AF XY: 0.570 AC XY: 42297 AN XY: 74246

African (AFR) AF: 0.477 AC: 19741 AN: 41390

American (AMR) AF: 0.586 AC: 8950 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1768 AN: 3470

East Asian (EAS) AF: 0.510 AC: 2618 AN: 5138

South Asian (SAS) AF: 0.569 AC: 2734 AN: 4806

European-Finnish (FIN) AF: 0.608 AC: 6417 AN: 10548

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42555 AN: 67972

Other (OTH) AF: 0.553 AC: 1169 AN: 2114

Alfa AF: 0.604 Hom.: 83243

Bravo AF: 0.563

Asia WGS AF: 0.588 AC: 2044 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 14, 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	-0.84
CADD	Benign	2.5
DANN	Benign	0.56
PhyloP100		0.32
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: rs2523; hg19: chr17-12895815;