NM_018127.7:c.1305-6dupC

Variant names:

• chr17-13000279-A-AG
• rs200410915
• NM_018127.7:c.1305-6dupC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018127.7(ELAC2):​c.1305-6dupC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0081 in 1,613,398 control chromosomes in the GnomAD database, including 633 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0082 (50 hom., cov: 33)
  • Exomes 𝑓: 0.0081 (583 hom.)
• Consequence: ELAC2 NM_018127.7 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103
• Publications: 1 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 -10 ACMG points.

• BP6: Variant 17-13000279-A-AG is Benign according to our data. Variant chr17-13000279-A-AG is described in ClinVar as Benign. ClinVar VariationId is 541492.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 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.1305-6dupC		splice_region intron	N/A	NP_060597.4
	ELAC2	NM_173717.2		c.1302-6dupC		splice_region intron	N/A	NP_776065.1
	ELAC2	NM_001165962.2		c.1185-6dupC		splice_region intron	N/A	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.1305-6dupC		splice_region intron	N/A	ENSP00000337445.4	Q9BQ52-1
	ELAC2	ENST00000446899.5	TSL:5	c.642-6dupC		splice_region intron	N/A	ENSP00000406192.1	H7C2I4
	ELAC2	ENST00000923774.1		c.1407-6dupC		splice_region intron	N/A	ENSP00000593833.1

Frequencies

GnomAD3 genomes AF: 0.00821 AC: 1249 AN: 152212 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0523

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00557 AC: 1386 AN: 248958 AF XY: 0.00580

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0463

Gnomad FIN exome AF: 0.00538

Gnomad NFE exome AF: 0.000308

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00809 AC: 11821 AN: 1461068 Hom.: 583 Cov.: 30 AF XY: 0.00908 AC XY: 6603 AN XY: 726910

African (AFR) AF: 0.000209 AC: 7 AN: 33466

American (AMR) AF: 0.000291 AC: 13 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26130

East Asian (EAS) AF: 0.145 AC: 5751 AN: 39686

South Asian (SAS) AF: 0.0456 AC: 3934 AN: 86232

European-Finnish (FIN) AF: 0.0195 AC: 1040 AN: 53340

Middle Eastern (MID) AF: 0.00331 AC: 19 AN: 5746

European-Non Finnish (NFE) AF: 0.000355 AC: 394 AN: 1111368

Other (OTH) AF: 0.0109 AC: 656 AN: 60378

GnomAD4 genome AF: 0.00820 AC: 1249 AN: 152330 Hom.: 50 Cov.: 33 AF XY: 0.0103 AC XY: 770 AN XY: 74472

African (AFR) AF: 0.000433 AC: 18 AN: 41580

American (AMR) AF: 0.00176 AC: 27 AN: 15304

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

East Asian (EAS) AF: 0.121 AC: 627 AN: 5170

South Asian (SAS) AF: 0.0522 AC: 252 AN: 4830

European-Finnish (FIN) AF: 0.0238 AC: 253 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000926 AC: 63 AN: 68038

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00333 Hom.: 1

Asia WGS AF: 0.0680 AC: 234 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Combined oxidative phosphorylation defect type 17 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.10
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: rs200410915; hg19: chr17-12903596;