rs1044569

Variant names:

• chr17-12992612-G-A
• rs1044569
• NM_018127.7:c.*206C>T

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.*206C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 606,774 control chromosomes in the GnomAD database, including 105,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (25330 hom., cov: 30)
  • Exomes 𝑓: 0.59 (80540 hom.)
• Consequence: ELAC2 NM_018127.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.22
• Publications: 29 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• 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=-0.89).
• BP6: Variant 17-12992612-G-A is Benign according to our data. Variant chr17-12992612-G-A is described in ClinVar as Benign. ClinVar VariationId is 1234592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

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.*206C>T		3_prime_UTR	Exon 24 of 24	NP_060597.4
	ELAC2	NM_173717.2		c.*206C>T		3_prime_UTR	Exon 24 of 24	NP_776065.1
	ELAC2	NM_001165962.2		c.*206C>T		3_prime_UTR	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.*206C>T		3_prime_UTR	Exon 24 of 24	ENSP00000337445.4	Q9BQ52-1
	ELAC2	ENST00000584650.5	TSL:2	c.*206C>T		splice_region	Exon 19 of 19	ENSP00000463740.2	E7ES68
	ELAC2	ENST00000923774.1		c.*206C>T		3_prime_UTR	Exon 25 of 25	ENSP00000593833.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87335 AN: 151408 Hom.: 25306 Cov.: 30

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.561

GnomAD4 exome AF: 0.592 AC: 269642 AN: 455248 Hom.: 80540 Cov.: 5 AF XY: 0.590 AC XY: 140186 AN XY: 237418

African (AFR) AF: 0.506 AC: 6357 AN: 12572

American (AMR) AF: 0.590 AC: 10932 AN: 18544

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 6906 AN: 13672

East Asian (EAS) AF: 0.461 AC: 14127 AN: 30636

South Asian (SAS) AF: 0.551 AC: 24371 AN: 44246

European-Finnish (FIN) AF: 0.599 AC: 17330 AN: 28934

Middle Eastern (MID) AF: 0.528 AC: 1036 AN: 1962

European-Non Finnish (NFE) AF: 0.622 AC: 173236 AN: 278610

Other (OTH) AF: 0.589 AC: 15347 AN: 26072

GnomAD4 genome AF: 0.577 AC: 87408 AN: 151526 Hom.: 25330 Cov.: 30 AF XY: 0.577 AC XY: 42686 AN XY: 74004

African (AFR) AF: 0.508 AC: 20964 AN: 41246

American (AMR) AF: 0.590 AC: 8985 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3470

East Asian (EAS) AF: 0.512 AC: 2608 AN: 5096

South Asian (SAS) AF: 0.571 AC: 2735 AN: 4794

European-Finnish (FIN) AF: 0.594 AC: 6221 AN: 10468

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.623 AC: 42323 AN: 67910

Other (OTH) AF: 0.561 AC: 1180 AN: 2104

Alfa AF: 0.607 Hom.: 36363

Bravo AF: 0.572

Asia WGS AF: 0.588 AC: 2046 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.54
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.98
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: rs1044569; hg19: chr17-12895929; COSMIC: COSV52391922; COSMIC: COSV52391922;