rs200410915

chr17-13000279-A-AG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018127.7(ELAC2):c.1305-6_1305-5insC variant causes a splice region, splice polypyrimidine tract, 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. 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, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELAC2	NM_018127.7	c.1305-6_1305-5insC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000338034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELAC2	ENST00000338034.9	c.1305-6_1305-5insC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018127.7	P2

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

GnomAD3 exomes AF: 0.00557 AC: 1386 AN: 248958 Hom.: 125 AF XY: 0.00580 AC XY: 779 AN XY: 134332

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 SAS exome AF: 0.0138

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

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.0456

Gnomad4 FIN exome AF: 0.0195

Gnomad4 NFE exome AF: 0.000355

Gnomad4 OTH exome AF: 0.0109

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

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0522

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.000926

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00333 Hom.: 1

Asia WGS AF: 0.0680 AC: 234 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Combined oxidative phosphorylation defect type 17 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 08, 2020

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs200410915; hg19: chr17-12903596;