chr17-13017774-C-T

Variant names:

• chr17-13017774-C-T
• rs2286334
• NM_018127.7:c.174G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_018127.7(ELAC2):​c.174G>A​(p.Val58Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,611,200 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V58V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0026 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (125 hom.)
• Consequence: ELAC2 NM_018127.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.00800
• Publications: 7 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 17-13017774-C-T is Benign according to our data. Variant chr17-13017774-C-T is described in ClinVar as Benign. ClinVar VariationId is 382955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.008 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018127.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC2	NM_018127.7	MANE Select	c.174G>A	p.Val58Val	synonymous	Exon 1 of 24	NP_060597.4
	ELAC2	NM_173717.2		c.174G>A	p.Val58Val	synonymous	Exon 1 of 24	NP_776065.1
	ELAC2	NM_001165962.2		c.174G>A	p.Val58Val	synonymous	Exon 1 of 23	NP_001159434.1	Q9BQ52-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC2	ENST00000338034.9	TSL:1 MANE Select	c.174G>A	p.Val58Val	synonymous	Exon 1 of 24	ENSP00000337445.4	Q9BQ52-1
	ELAC2	ENST00000923774.1		c.174G>A	p.Val58Val	synonymous	Exon 1 of 25	ENSP00000593833.1
	ELAC2	ENST00000860253.1		c.174G>A	p.Val58Val	synonymous	Exon 1 of 25	ENSP00000530312.1

Frequencies

GnomAD3 genomes AF: 0.00259 AC: 395 AN: 152248 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0580

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000558

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00550 AC: 1275 AN: 231630 AF XY: 0.00495

Gnomad AFR exome AF: 0.000217

Gnomad AMR exome AF: 0.000325

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0618

Gnomad FIN exome AF: 0.00165

Gnomad NFE exome AF: 0.000799

Gnomad OTH exome AF: 0.00283

GnomAD4 exome AF: 0.00254 AC: 3712 AN: 1458834 Hom.: 125 Cov.: 31 AF XY: 0.00254 AC XY: 1846 AN XY: 725588

African (AFR) AF: 0.000149 AC: 5 AN: 33462

American (AMR) AF: 0.000225 AC: 10 AN: 44528

Ashkenazi Jewish (ASJ) AF: 0.0000768 AC: 2 AN: 26030

East Asian (EAS) AF: 0.0696 AC: 2756 AN: 39612

South Asian (SAS) AF: 0.00164 AC: 141 AN: 85858

European-Finnish (FIN) AF: 0.00199 AC: 104 AN: 52248

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5760

European-Non Finnish (NFE) AF: 0.000380 AC: 422 AN: 1111150

Other (OTH) AF: 0.00434 AC: 261 AN: 60186

GnomAD4 genome AF: 0.00259 AC: 394 AN: 152366 Hom.: 11 Cov.: 32 AF XY: 0.00271 AC XY: 202 AN XY: 74506

African (AFR) AF: 0.0000481 AC: 2 AN: 41594

American (AMR) AF: 0.00131 AC: 20 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0579 AC: 300 AN: 5178

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68036

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.000727 Hom.: 0

Bravo AF: 0.00287

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Combined oxidative phosphorylation defect type 17 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Prostate cancer, hereditary, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		-0.0080
PromoterAI		0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2286334; hg19: chr17-12921091;