17-12992612-G-A

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.*206C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 606,774 control chromosomes in the GnomAD database, including 105,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (25330 hom., cov: 30)
  • Exomes 𝑓: 0.59 (80540 hom.)
• Consequence: ELAC2 NM_018127.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22

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=-0.89).
• BP6: Variant 17-12992612-G-A is Benign according to our data. Variant chr17-12992612-G-A is described in ClinVar as [Benign]. Clinvar id is 1234592.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELAC2	NM_018127.7	c.*206C>T		3_prime_UTR_variant	24/24	ENST00000338034.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELAC2	ENST00000338034.9	c.*206C>T		3_prime_UTR_variant	24/24	1	NM_018127.7	P2

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87335 AN: 151408 Hom.: 25306 Cov.: 30

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.561

GnomAD4 exome AF: 0.592 AC: 269642 AN: 455248 Hom.: 80540 Cov.: 5 AF XY: 0.590 AC XY: 140186 AN XY: 237418

Gnomad4 AFR exome AF: 0.506

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.505

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.551

Gnomad4 FIN exome AF: 0.599

Gnomad4 NFE exome AF: 0.622

Gnomad4 OTH exome AF: 0.589

GnomAD4 genome AF: 0.577 AC: 87408 AN: 151526 Hom.: 25330 Cov.: 30 AF XY: 0.577 AC XY: 42686 AN XY: 74004

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.561

Alfa AF: 0.611 Hom.: 28021

Bravo AF: 0.572

Asia WGS AF: 0.588 AC: 2046 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 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.18
Dann	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.98

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: rs1044569; hg19: chr17-12895929; COSMIC: COSV52391922; COSMIC: COSV52391922;