rs878855051

Variant names:

• chr17-12992883-C-CATCCTCCAGGCCGCCTGCCAGCTCCCTGGACAGGAGGGCCGCCCGCACCTGCCGCAGCCCCCG
• rs878855051
• NM_018127.7:c.2415_2416insCGGGGGCTGCGGCAGGTGCGGGCGGCCCTCCTGTCCAGGGAGCTGGCAGGCGGCCTGGAGGAT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. 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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_018127.7.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018127.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC2	NM_018127.7	MANE Select	c.2415_2416insCGGGGGCTGCGGCAGGTGCGGGCGGCCCTCCTGTCCAGGGAGCTGGCAGGCGGCCTGGAGGAT	p.Asp805_Gly806insArgGlyLeuArgGlnValArgAlaAlaLeuLeuSerArgGluLeuAlaGlyGlyLeuGluAsp	conservative_inframe_insertion	Exon 24 of 24	NP_060597.4
	ELAC2	NM_173717.2		c.2412_2413insCGGGGGCTGCGGCAGGTGCGGGCGGCCCTCCTGTCCAGGGAGCTGGCAGGCGGCCTGGAGGAT	p.Asp804_Gly805insArgGlyLeuArgGlnValArgAlaAlaLeuLeuSerArgGluLeuAlaGlyGlyLeuGluAsp	conservative_inframe_insertion	Exon 24 of 24	NP_776065.1
	ELAC2	NM_001165962.2		c.2295_2296insCGGGGGCTGCGGCAGGTGCGGGCGGCCCTCCTGTCCAGGGAGCTGGCAGGCGGCCTGGAGGAT	p.Asp765_Gly766insArgGlyLeuArgGlnValArgAlaAlaLeuLeuSerArgGluLeuAlaGlyGlyLeuGluAsp	conservative_inframe_insertion	Exon 23 of 23	NP_001159434.1	Q9BQ52-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC2	ENST00000338034.9	TSL:1 MANE Select	c.2415_2416insCGGGGGCTGCGGCAGGTGCGGGCGGCCCTCCTGTCCAGGGAGCTGGCAGGCGGCCTGGAGGAT	p.Asp805_Gly806insArgGlyLeuArgGlnValArgAlaAlaLeuLeuSerArgGluLeuAlaGlyGlyLeuGluAsp	conservative_inframe_insertion	Exon 24 of 24	ENSP00000337445.4	Q9BQ52-1
	ELAC2	ENST00000923774.1		c.2517_2518insCGGGGGCTGCGGCAGGTGCGGGCGGCCCTCCTGTCCAGGGAGCTGGCAGGCGGCCTGGAGGAT	p.Asp839_Gly840insArgGlyLeuArgGlnValArgAlaAlaLeuLeuSerArgGluLeuAlaGlyGlyLeuGluAsp	conservative_inframe_insertion	Exon 25 of 25	ENSP00000593833.1
	ELAC2	ENST00000860253.1		c.2439_2440insCGGGGGCTGCGGCAGGTGCGGGCGGCCCTCCTGTCCAGGGAGCTGGCAGGCGGCCTGGAGGAT	p.Asp813_Gly814insArgGlyLeuArgGlnValArgAlaAlaLeuLeuSerArgGluLeuAlaGlyGlyLeuGluAsp	conservative_inframe_insertion	Exon 25 of 25	ENSP00000530312.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Combined oxidative phosphorylation defect type 17 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.69

Splicing

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

Other links and lift over

dbSNP: rs878855051; hg19: chr17-12896200;