17-12992924-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ELAC2 NM_018127.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72

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 Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELAC2	NM_018127.7	c.2375C>G	p.Ala792Gly	missense_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.2375C>G	p.Ala792Gly	missense_variant	Exon 24 of 24	1	NM_018127.7	ENSP00000337445.4

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 v4.3

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;T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.88	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.083	T;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.84	P;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

Publications

LitVar

Other links and lift over

dbSNP: rs767378629; hg19: chr17-12896241;