Variant 22-41518589-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001098.3(ACO2):c.1032+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,596,706 control chromosomes in the GnomAD database, including 66,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 11416 hom., cov: 31)

Exomes 𝑓: 0.25 ( 55096 hom. )

Consequence

ACO2
NM_001098.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.26

Variant links:

Genes affected

ACO2 (HGNC:118): (aconitase 2) The protein encoded by this gene belongs to the aconitase/IPM isomerase family. It is an enzyme that catalyzes the interconversion of citrate to isocitrate via cis-aconitate in the second step of the TCA cycle. This protein is encoded in the nucleus and functions in the mitochondrion. It was found to be one of the mitochondrial matrix proteins that are preferentially degraded by the serine protease 15(PRSS15), also known as Lon protease, after oxidative modification. [provided by RefSeq, Jul 2008]

ACO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 22-41518589-C-T is Benign according to our data. Variant chr22-41518589-C-T is described in ClinVar as [Benign]. Clinvar id is 136263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-41518589-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACO2	NM_001098.3 linkuse as main transcript	c.1032+17C>T		intron_variant		ENST00000216254.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACO2	ENST00000216254.9 linkuse as main transcript	c.1032+17C>T		intron_variant		1	NM_001098.3	P3

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53440

AN:

151762

Hom.:

11381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.545

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.318

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.350

GnomAD3 exomes

AF:

0.351

AC:

88002

AN:

250906

Hom.:

19667

AF XY:

0.336

AC XY:

45509

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.551

Gnomad AMR exome

AF:

0.657

Gnomad ASJ exome

AF:

0.317

Gnomad EAS exome

AF:

0.574

Gnomad SAS exome

AF:

0.382

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.323

GnomAD4 exome

AF:

0.251

AC:

363278

AN:

1444826

Hom.:

55096

Cov.:

AF XY:

0.253

AC XY:

182158

AN XY:

719894

show subpopulations

Gnomad4 AFR exome

AF:

0.561

Gnomad4 AMR exome

AF:

0.638

Gnomad4 ASJ exome

AF:

0.313

Gnomad4 EAS exome

AF:

0.456

Gnomad4 SAS exome

AF:

0.385

Gnomad4 FIN exome

AF:

0.258

Gnomad4 NFE exome

AF:

0.204

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.352

AC:

53531

AN:

151880

Hom.:

11416

Cov.:

AF XY:

0.360

AC XY:

26762

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.546

Gnomad4 AMR

AF:

0.493

Gnomad4 ASJ

AF:

0.308

Gnomad4 EAS

AF:

0.533

Gnomad4 SAS

AF:

0.409

Gnomad4 FIN

AF:

0.258

Gnomad4 NFE

AF:

0.203

Gnomad4 OTH

AF:

0.347

Alfa

AF:

0.239

Hom.:

1528

Bravo

AF:

0.384

Asia WGS

AF:

0.417

AC:

1448

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Optic atrophy 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Infantile cerebellar-retinal degeneration

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.76

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over