rs7217826

Variant names:

• chr17-12993810-G-A
• rs7217826
• NM_018127.7:c.2130C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-12993810-G-A
• chr17-12993810-G-C
• chr17-12993810-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018127.7(ELAC2):​c.2130C>T​(p.Ser710Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,614,156 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (90 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (91 hom.)
• Consequence: ELAC2 NM_018127.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.77
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-12993810-G-A is Benign according to our data. Variant chr17-12993810-G-A is described in ClinVar as Benign. ClinVar VariationId is 381413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.77 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0661 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.2130C>T	p.Ser710Ser	synonymous	Exon 23 of 24	NP_060597.4
	ELAC2	NM_173717.2		c.2127C>T	p.Ser709Ser	synonymous	Exon 23 of 24	NP_776065.1
	ELAC2	NM_001165962.2		c.2010C>T	p.Ser670Ser	synonymous	Exon 22 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.2130C>T	p.Ser710Ser	synonymous	Exon 23 of 24	ENSP00000337445.4	Q9BQ52-1
	ELAC2	ENST00000923774.1		c.2232C>T	p.Ser744Ser	synonymous	Exon 24 of 25	ENSP00000593833.1
	ELAC2	ENST00000860253.1		c.2154C>T	p.Ser718Ser	synonymous	Exon 24 of 25	ENSP00000530312.1

Frequencies

GnomAD3 genomes AF: 0.0195 AC: 2974 AN: 152160 Hom.: 88 Cov.: 33

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0168

GnomAD2 exomes AF: 0.00539 AC: 1356 AN: 251352 AF XY: 0.00404

Gnomad AFR exome AF: 0.0724

Gnomad AMR exome AF: 0.00379

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00207 AC: 3030 AN: 1461878 Hom.: 91 Cov.: 31 AF XY: 0.00181 AC XY: 1313 AN XY: 727238

African (AFR) AF: 0.0698 AC: 2337 AN: 33480

American (AMR) AF: 0.00394 AC: 176 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.000181 AC: 201 AN: 1112008

Other (OTH) AF: 0.00467 AC: 282 AN: 60396

GnomAD4 genome AF: 0.0196 AC: 2981 AN: 152278 Hom.: 90 Cov.: 33 AF XY: 0.0192 AC XY: 1432 AN XY: 74450

African (AFR) AF: 0.0682 AC: 2833 AN: 41548

American (AMR) AF: 0.00575 AC: 88 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68026

Other (OTH) AF: 0.0166 AC: 35 AN: 2106

Alfa AF: 0.00834 Hom.: 60

Bravo AF: 0.0224

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000474

ClinVar

ClinVar submissions as Germline

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	-0.79
CADD	Benign	0.22
DANN	Benign	0.79
PhyloP100		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs7217826; hg19: chr17-12897127;