NM_018127.7:c.2375C>G

Variant names:

• chr17-12992924-G-C
• rs767378629
• NM_018127.7:c.2375C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018127.7(ELAC2):​c.2375C>G​(p.Ala792Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A792V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ELAC2 NM_018127.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12174854).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC2	NM_018127.7	MANE Select	c.2375C>G	p.Ala792Gly	missense	Exon 24 of 24	NP_060597.4
	ELAC2	NM_173717.2		c.2372C>G	p.Ala791Gly	missense	Exon 24 of 24	NP_776065.1
	ELAC2	NM_001165962.2		c.2255C>G	p.Ala752Gly	missense	Exon 23 of 23	NP_001159434.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC2	ENST00000338034.9	TSL:1 MANE Select	c.2375C>G	p.Ala792Gly	missense	Exon 24 of 24	ENSP00000337445.4
	ELAC2	ENST00000395962.6	TSL:2	c.2318C>G	p.Ala773Gly	missense	Exon 24 of 24	ENSP00000379291.1
	ELAC2	ENST00000426905.7	TSL:2	c.2255C>G	p.Ala752Gly	missense	Exon 23 of 23	ENSP00000405223.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.87
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.7
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.13
Sift	Benign	0.083	T
Sift4G	Benign	0.35	T
Polyphen		0.84	P
Vest4		0.10
MutPred		0.19		Loss of stability (P = 0.137)
MVP		0.68
MPC		0.41
ClinPred		0.33	T
GERP RS		0.60
Varity_R		0.044
gMVP		0.31

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: rs767378629; hg19: chr17-12896241;