17-12992538-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018127.7(ELAC2):c.*280T>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 0.883 in 517,234 control chromosomes in the GnomAD database, including 203,662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (55708 hom., cov: 31)
  • Exomes 𝑓: 0.90 (147954 hom.)
• Consequence: ELAC2 NM_018127.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.468

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-12992538-A-T is Benign according to our data. Variant chr17-12992538-A-T is described in ClinVar as [Benign]. Clinvar id is 1287594.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELAC2	NM_018127.7	c.*280T>A		3_prime_UTR_variant	24/24	ENST00000338034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELAC2	ENST00000338034.9	c.*280T>A		3_prime_UTR_variant	24/24	1	NM_018127.7	P2

Frequencies

GnomAD3 genomes AF: 0.850 AC: 129091 AN: 151920 Hom.: 55672 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.862

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.843

GnomAD4 exome AF: 0.897 AC: 327456 AN: 365196 Hom.: 147954 Cov.: 2 AF XY: 0.898 AC XY: 170548 AN XY: 189838

Gnomad4 AFR exome AF: 0.703

Gnomad4 AMR exome AF: 0.854

Gnomad4 ASJ exome AF: 0.890

Gnomad4 EAS exome AF: 0.669

Gnomad4 SAS exome AF: 0.914

Gnomad4 FIN exome AF: 0.944

Gnomad4 NFE exome AF: 0.930

Gnomad4 OTH exome AF: 0.888

GnomAD4 genome AF: 0.850 AC: 129179 AN: 152038 Hom.: 55708 Cov.: 31 AF XY: 0.850 AC XY: 63208 AN XY: 74332

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.918

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.932

Gnomad4 OTH AF: 0.842

Alfa AF: 0.893 Hom.: 3079

Bravo AF: 0.833

Asia WGS AF: 0.822 AC: 2860 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.91
Dann	Benign	0.72

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: rs6949; hg19: chr17-12895855;