rs202202906

Variant names:

• chr6-41061332-C-T
• rs202202906
• NM_006789.4:c.136C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-41061332-C-T
• chr6-41061332-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.80
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.927

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006789.4. 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
	APOBEC2	NM_006789.4	MANE Select	c.136C>T	p.Arg46Trp	missense	Exon 2 of 3	NP_006780.1	Q9Y235

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC2	ENST00000244669.3	TSL:1 MANE Select	c.136C>T	p.Arg46Trp	missense	Exon 2 of 3	ENSP00000244669.2	Q9Y235
	APOBEC2	ENST00000899065.1		c.136C>T	p.Arg46Trp	missense	Exon 2 of 2	ENSP00000569124.1
	OARD1	ENST00000482853.5	TSL:2	n.144+8744G>A		intron	N/A	ENSP00000420472.1	H7C5Q1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152118 Hom.: 0 Cov.: 31

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

GnomAD2 exomes AF: 0.0000219 AC: 4 AN: 182366 AF XY: 0.0000104

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 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

African (AFR) AF: 0.000131 AC: 4 AN: 30572

American (AMR) AF: 0.0000322 AC: 1 AN: 31058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20268

East Asian (EAS) AF: 0.0000514 AC: 2 AN: 38948

South Asian (SAS) AF: 0.00 AC: 0 AN: 71152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5338

European-Non Finnish (NFE) AF: 0.0000402 AC: 43 AN: 1069874

Other (OTH) AF: 0.0000354 AC: 2 AN: 56512

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152118 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00000831 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.8
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
Mutation Taster		=40/60	disease causing

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

Other links and lift over

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