Variant 6-41053411-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006789.4(APOBEC2):c.64G>A(p.Glu22Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

APOBEC2
NM_006789.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83

Variant links:

Genes affected

APOBEC2 (HGNC:605): (apolipoprotein B mRNA editing enzyme catalytic subunit 2) Enables cytidine deaminase activity and identical protein binding activity. Involved in DNA demethylation. Acts upstream of or within cytidine to uridine editing. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

APOBEC2 links:

OARD1 (HGNC:21257): (O-acyl-ADP-ribose deacylase 1) The protein encoded by this gene is a deacylase that can convert O-acetyl-ADP-ribose to ADP-ribose and acetate, O-propionyl-ADP-ribose to ADP-ribose and propionate, and O-butyryl-ADP-ribose to ADP-ribose and butyrate. The ADP-ribose product is able to inhibit these reactions through a competitive feedback loop. [provided by RefSeq, Jul 2016]

OARD1 links:

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ACMG classification

Classification made for transcript

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=0.12870851).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC2	NM_006789.4 linkuse as main transcript	c.64G>A	p.Glu22Lys	missense_variant	1/3	ENST00000244669.3	NP_006780.1	Q9Y235

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC2	ENST00000244669.3 linkuse as main transcript	c.64G>A	p.Glu22Lys	missense_variant	1/3	1	NM_006789.4	ENSP00000244669.2		Q9Y235
OARD1	ENST00000482853.5 linkuse as main transcript	n.145-1048C>T		intron_variant		2		ENSP00000420472.1		H7C5Q1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251324

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 30, 2024

The c.64G>A (p.E22K) alteration is located in exon 1 (coding exon 1) of the APOBEC2 gene. This alteration results from a G to A substitution at nucleotide position 64, causing the glutamic acid (E) at amino acid position 22 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

Eigen

Benign

-0.044

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.72

M_CAP

Benign

0.0076

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.71

REVEL

Benign

0.034

Sift

Benign

0.13

Sift4G

Benign

0.26

Polyphen

0.010

Vest4

0.15

MutPred

0.24

Gain of ubiquitination at E22 (P = 0.0077);

MVP

0.65

MPC

0.070

ClinPred

0.077

GERP RS

5.6

Varity_R

0.18

gMVP

0.59

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