17-12992785-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_018127.7(ELAC2):c.*33G>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 0.00283 in 1,608,572 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (13 hom.)
• Consequence: ELAC2 NM_018127.7 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.132

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=-0.8).
• BP6: Variant 17-12992785-C-A is Benign according to our data. Variant chr17-12992785-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1203288.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00222 (338/152278) while in subpopulation SAS AF= 0.00415 (20/4824). AF 95% confidence interval is 0.0029. There are 0 homozygotes in gnomad4. There are 167 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELAC2	NM_018127.7	c.*33G>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.*33G>T		3_prime_UTR_variant	24/24	1	NM_018127.7	P2

Frequencies

GnomAD3 genomes AF: 0.00223 AC: 339 AN: 152160 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00325

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00295 AC: 740 AN: 250814 Hom.: 5 AF XY: 0.00324 AC XY: 439 AN XY: 135618

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00318

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00591

Gnomad FIN exome AF: 0.00135

Gnomad NFE exome AF: 0.00334

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00289 AC: 4211 AN: 1456294 Hom.: 13 Cov.: 31 AF XY: 0.00304 AC XY: 2202 AN XY: 724738

Gnomad4 AFR exome AF: 0.000300

Gnomad4 AMR exome AF: 0.00347

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00628

Gnomad4 FIN exome AF: 0.00133

Gnomad4 NFE exome AF: 0.00291

Gnomad4 OTH exome AF: 0.00282

GnomAD4 genome AF: 0.00222 AC: 338 AN: 152278 Hom.: 0 Cov.: 33 AF XY: 0.00224 AC XY: 167 AN XY: 74454

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00325

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00261 Hom.: 0

Bravo AF: 0.00236

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 06, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.52
Dann	Benign	0.73

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: rs200771997; hg19: chr17-12896102;