Variant 6-41061407-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_006789.4(APOBEC2):c.211T>A(p.Cys71Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

APOBEC2
NM_006789.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.61

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.971

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC2	NM_006789.4 linkuse as main transcript	c.211T>A	p.Cys71Ser	missense_variant	2/3	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.211T>A	p.Cys71Ser	missense_variant	2/3	1	NM_006789.4	ENSP00000244669.2		Q9Y235
OARD1	ENST00000482853.5 linkuse as main transcript	n.144+8669A>T		intron_variant		2		ENSP00000420472.1		H7C5Q1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000823

AC:

AN:

243086

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

131274

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1452622

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Nov 11, 2024

The c.211T>A (p.C71S) alteration is located in exon 2 (coding exon 2) of the APOBEC2 gene. This alteration results from a T to A substitution at nucleotide position 211, causing the cysteine (C) at amino acid position 71 to be replaced by a serine (S). 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

0.99

BayesDel_addAF

Pathogenic

0.47

BayesDel_noAF

Pathogenic

0.44

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.43

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.31

MetaRNN

Pathogenic

0.97

MetaSVM

Pathogenic

0.86

MutationAssessor

Pathogenic

3.6

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-9.4

REVEL

Pathogenic

0.93

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.86

MutPred

0.89

Loss of stability (P = 0.0073);

MVP

0.95

MPC

0.40

ClinPred

1.0

GERP RS

5.7

Varity_R

0.98

gMVP

0.94

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