15-29054048-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001353788.2(APBA2):c.164G>A(p.Ser55Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00578 in 1,613,828 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 53 hom. )

Consequence

APBA2
NM_001353788.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 7.96

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073262453).

BP6

Variant 15-29054048-G-A is Benign according to our data. Variant chr15-29054048-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 715589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBA2	NM_001353788.2 link	c.164G>A	p.Ser55Asn	missense_variant	Exon 4 of 15	ENST00000683413.1	NP_001340717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBA2	ENST00000683413.1 link	c.164G>A	p.Ser55Asn	missense_variant	Exon 4 of 15		NM_001353788.2	ENSP00000507394.1		Q99767-1

Frequencies

GnomAD3 genomes

AF:

0.00499

AC:

759

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00761

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00527

AC:

1323

AN:

251160

Hom.:

AF XY:

0.00549

AC XY:

746

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.000925

Gnomad AMR exome

AF:

0.00465

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00559

Gnomad FIN exome

AF:

0.00360

Gnomad NFE exome

AF:

0.00740

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00586

AC:

8562

AN:

1461542

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

4358

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00510

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00606

Gnomad4 FIN exome

AF:

0.00446

Gnomad4 NFE exome

AF:

0.00644

Gnomad4 OTH exome

AF:

0.00532

GnomAD4 genome

AF:

0.00498

AC:

759

AN:

152286

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

351

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.00762

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00629

Hom.:

Bravo

AF:

0.00447

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00547

AC:

ExAC

AF:

0.00586

AC:

711

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00671

EpiControl

AF:

0.00622

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

APBA2: BP4, BS2 -

May 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

APBA2-related disorder

Benign:1

Jun 11, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

0.10

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

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

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

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

M_CAP

Uncertain

0.099

MetaRNN

Benign

0.0073

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

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.2

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

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.14

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

REVEL

Benign

0.13

Sift

Uncertain

0.0010

D;D;D;D;D;D;D;D

Sift4G

Benign

0.41

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

Polyphen

0.99

D;D;.;.;D;.;.;.

Vest4

0.38

MVP

0.70

MPC

0.95

ClinPred

0.042

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.16

gMVP

0.23

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