chr22-41499405-G-A

Position:

• chr22-41499405-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001098.3(ACO2):​c.37-321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,182 control chromosomes in the GnomAD database, including 1,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1732 hom., cov: 32)
• Consequence: ACO2 NM_001098.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.190

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 22-41499405-G-A is Benign according to our data. Variant chr22-41499405-G-A is described in ClinVar as [Benign]. Clinvar id is 1273288.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACO2	NM_001098.3	c.37-321G>A		intron_variant		ENST00000216254.9	NP_001089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACO2	ENST00000216254.9	c.37-321G>A		intron_variant		1	NM_001098.3	ENSP00000216254	P3

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20106 AN: 152064 Hom.: 1734 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.132 AC: 20097 AN: 152182 Hom.: 1732 Cov.: 32 AF XY: 0.131 AC XY: 9770 AN XY: 74396

Gnomad4 AFR AF: 0.0357

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.133

Alfa AF: 0.174 Hom.: 5216

Bravo AF: 0.126

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.61

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: rs2076196; hg19: chr22-41895409;