17-12992538-A-T

Variant names:

• chr17-12992538-A-T
• rs6949
• NM_018127.7:c.*280T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.468
• Publications: 9 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ELAC2	NM_018127.7	c.*280T>A		3_prime_UTR_variant	Exon 24 of 24	ENST00000338034.9	NP_060597.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9	c.*280T>A		3_prime_UTR_variant	Exon 24 of 24	1	NM_018127.7	ENSP00000337445.4

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

African (AFR) AF: 0.703 AC: 7951 AN: 11304

American (AMR) AF: 0.854 AC: 13030 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 10539 AN: 11846

East Asian (EAS) AF: 0.669 AC: 16921 AN: 25300

South Asian (SAS) AF: 0.914 AC: 35960 AN: 39364

European-Finnish (FIN) AF: 0.944 AC: 19652 AN: 20828

Middle Eastern (MID) AF: 0.872 AC: 1441 AN: 1652

European-Non Finnish (NFE) AF: 0.930 AC: 202664 AN: 217902

Other (OTH) AF: 0.888 AC: 19298 AN: 21734

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

African (AFR) AF: 0.700 AC: 28996 AN: 41442

American (AMR) AF: 0.843 AC: 12868 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3098 AN: 3472

East Asian (EAS) AF: 0.694 AC: 3572 AN: 5150

South Asian (SAS) AF: 0.918 AC: 4423 AN: 4820

European-Finnish (FIN) AF: 0.943 AC: 9973 AN: 10576

Middle Eastern (MID) AF: 0.866 AC: 251 AN: 290

European-Non Finnish (NFE) AF: 0.932 AC: 63350 AN: 68004

Other (OTH) AF: 0.842 AC: 1779 AN: 2112

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.91
DANN	Benign	0.72
PhyloP100		-0.47
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: rs6949; hg19: chr17-12895855;