Variant chr15-29054039-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001353788.2(APBA2):c.155G>A(p.Arg52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,613,814 control chromosomes in the GnomAD database, including 290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 16 hom., cov: 32)

Exomes 𝑓: 0.017 ( 274 hom. )

Consequence

APBA2
NM_001353788.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.24

Variant links:

Genes affected

APBA2 (HGNC:579): (amyloid beta precursor protein binding family A member 2) The protein encoded by this gene is a member of the X11 protein family. It is a neuronal adapter protein that interacts with the Alzheimer's disease amyloid precursor protein (APP). It stabilizes APP and inhibits production of proteolytic APP fragments including the A beta peptide that is deposited in the brains of Alzheimer's disease patients. This gene product is believed to be involved in signal transduction processes. It is also regarded as a putative vesicular trafficking protein in the brain that can form a complex with the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. [provided by RefSeq, Jul 2017]

APBA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037463903).

BP6

Variant 15-29054039-G-A is Benign according to our data. Variant chr15-29054039-G-A is described in ClinVar as [Benign]. Clinvar id is 3037758.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0125 (1898/152268) while in subpopulation NFE AF= 0.019 (1291/68024). AF 95% confidence interval is 0.0181. There are 16 homozygotes in gnomad4. There are 925 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APBA2	NM_001353788.2 link	c.155G>A	p.Arg52Gln	missense_variant	4/15	ENST00000683413.1	NP_001340717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APBA2	ENST00000683413.1 link	c.155G>A	p.Arg52Gln	missense_variant	4/15		NM_001353788.2	ENSP00000507394.1		Q99767-1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1897

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00401

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00929

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00995

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0135

AC:

3381

AN:

251142

Hom.:

AF XY:

0.0140

AC XY:

1905

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00444

Gnomad AMR exome

AF:

0.00758

Gnomad ASJ exome

AF:

0.00903

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00817

Gnomad FIN exome

AF:

0.0170

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.0173

AC:

25265

AN:

1461546

Hom.:

274

Cov.:

AF XY:

0.0172

AC XY:

12481

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.00296

Gnomad4 AMR exome

AF:

0.00771

Gnomad4 ASJ exome

AF:

0.00945

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00827

Gnomad4 FIN exome

AF:

0.0172

Gnomad4 NFE exome

AF:

0.0197

Gnomad4 OTH exome

AF:

0.0159

GnomAD4 genome

AF:

0.0125

AC:

1898

AN:

152268

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

925

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00402

Gnomad4 AMR

AF:

0.00928

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00996

Gnomad4 FIN

AF:

0.0172

Gnomad4 NFE

AF:

0.0190

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0135

Hom.:

Bravo

AF:

0.0112

TwinsUK

AF:

0.0232

AC:

ALSPAC

AF:

0.0182

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0184

AC:

158

ExAC

AF:

0.0144

AC:

1746

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0175

EpiControl

AF:

0.0194

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

APBA2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;T;.;T;T;.;T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.82

.;.;.;T;T;T;T;T

MetaRNN

Benign

0.0037

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

M;M;M;.;M;M;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.19

N;N;N;D;N;N;D;N

REVEL

Benign

0.073

Sift

Benign

0.042

D;D;D;T;D;D;T;T

Sift4G

Benign

0.25

T;T;T;T;T;T;T;T

Polyphen

0.0010

B;B;.;.;B;.;.;.

Vest4

0.042

MPC

0.47

ClinPred

0.015

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.033

gMVP

0.34

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