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GeneBe

6-41061332-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006789.4(APOBEC2):c.136C>T(p.Arg46Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,526,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

APOBEC2
NM_006789.4 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PP3
?
    PP3 - Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.)
MetaRNN computational evidence supports a deleterious effect, 0.927

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
APOBEC2NM_006789.4 linkuse as main transcriptc.136C>T p.Arg46Trp missense_variant 2/3 ENST00000244669.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
APOBEC2ENST00000244669.3 linkuse as main transcriptc.136C>T p.Arg46Trp missense_variant 2/31 NM_006789.4 P1
OARD1ENST00000482853.5 linkuse as main transcriptc.145+8744G>A intron_variant, NMD_transcript_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00000657
AC:
1
AN:
152118
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000219
AC:
4
AN:
182366
Hom.:
0
AF XY:
0.0000104
AC XY:
1
AN XY:
95826
show subpopulations
Gnomad AFR exome
AF:
0.0000647
Gnomad AMR exome
AF:
0.0000443
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000618
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000114
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000378
AC:
52
AN:
1373886
Hom.:
0
Cov.:
31
AF XY:
0.0000356
AC XY:
24
AN XY:
673704
show subpopulations
Gnomad4 AFR exome
AF:
0.000131
Gnomad4 AMR exome
AF:
0.0000322
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000514
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000402
Gnomad4 OTH exome
AF:
0.0000354
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00000657
AC:
1
AN:
152118
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.00
AC:
0
ExAC
?
    Exome Aggregation Consortium database
AF:
0.00000831
AC:
1

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 submitterclinical testingAmbry GeneticsOct 26, 2022The c.136C>T (p.R46W) alteration is located in exon 2 (coding exon 2) of the APOBEC2 gene. This alteration results from a C to T substitution at nucleotide position 136, causing the arginine (R) at amino acid position 46 to be replaced by a tryptophan (W). 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
Pathogenic
0.65
BayesDel_addAF
Benign
-0.011
T
BayesDel_noAF
Uncertain
-0.070
Cadd
Benign
23
Dann
Pathogenic
1.0
DEOGEN2
Uncertain
0.43
T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.080
D
MetaRNN
Pathogenic
0.93
D
MetaSVM
Benign
-0.38
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-4.0
D
REVEL
Uncertain
0.59
Sift
Uncertain
0.0020
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.70
MutPred
0.76
Loss of loop (P = 0.0203);
MVP
0.84
MPC
0.36
ClinPred
0.94
D
GERP RS
2.8
Varity_R
0.65
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs202202906; hg19: chr6-41029071; COSMIC: COSV99775372; COSMIC: COSV99775372; API