rs878855051

Positions:

• chr17-12992883-C-CATCCTCCAGGCCGCCTGCCAGCTCCCTGGACAGGAGGGCCGCCCGCACCTGCCGCAGCCCCCG

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_018127.7(ELAC2):​c.2415_2416insCGGGGGCTGCGGCAGGTGCGGGCGGCCCTCCTGTCCAGGGAGCTGGCAGGCGGCCTGGAGGAT​(p.Asp805_Gly806insArgGlyLeuArgGlnValArgAlaAlaLeuLeuSerArgGluLeuAlaGlyGlyLeuGluAsp) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ELAC2 NM_018127.7 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.695

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_018127.7.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELAC2	NM_018127.7	c.2415_2416insCGGGGGCTGCGGCAGGTGCGGGCGGCCCTCCTGTCCAGGGAGCTGGCAGGCGGCCTGGAGGAT	p.Asp805_Gly806insArgGlyLeuArgGlnValArgAlaAlaLeuLeuSerArgGluLeuAlaGlyGlyLeuGluAsp	conservative_inframe_insertion	24/24	ENST00000338034.9	NP_060597.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELAC2	ENST00000338034.9	c.2415_2416insCGGGGGCTGCGGCAGGTGCGGGCGGCCCTCCTGTCCAGGGAGCTGGCAGGCGGCCTGGAGGAT	p.Asp805_Gly806insArgGlyLeuArgGlnValArgAlaAlaLeuLeuSerArgGluLeuAlaGlyGlyLeuGluAsp	conservative_inframe_insertion	24/24	1	NM_018127.7	ENSP00000337445.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Combined oxidative phosphorylation defect type 17 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2016

This sequence change inserts 63 nucleotides in exon 24 of the ELAC2 mRNA (c.2415_2416ins63). This leads to the insertion of 21 amino acid residue(s) in the ELAC2 protein (p.Asp805_Gly806ins21) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ELAC2-related disease. In summary, this is an in frame insertion with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs878855051; hg19: chr17-12896200;