rs141358568

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001353788.2(APBA2):c.170C>T(p.Ala57Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000693 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A57T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 0 hom. )

Consequence

APBA2
NM_001353788.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.211

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

epilepsy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

APBA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048353076).

BP6

Variant 15-29054054-C-T is Benign according to our data. Variant chr15-29054054-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3036076.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 103 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353788.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APBA2	NM_001353788.2	MANE Select	c.170C>T	p.Ala57Val	missense	Exon 4 of 15	NP_001340717.1	Q99767-1
APBA2	NM_001353789.2		c.170C>T	p.Ala57Val	missense	Exon 4 of 15	NP_001340718.1	Q99767-1
APBA2	NM_001353790.2		c.170C>T	p.Ala57Val	missense	Exon 4 of 15	NP_001340719.1	Q99767-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APBA2	ENST00000683413.1	MANE Select	c.170C>T	p.Ala57Val	missense	Exon 4 of 15	ENSP00000507394.1	Q99767-1
APBA2	ENST00000558259.5	TSL:1	c.170C>T	p.Ala57Val	missense	Exon 3 of 14	ENSP00000454171.1	Q99767-1
APBA2	ENST00000411764.5	TSL:1	c.170C>T	p.Ala57Val	missense	Exon 3 of 13	ENSP00000409312.1	Q99767-2

Frequencies

GnomAD3 genomes

AF:

0.000670

AC:

102

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.000462

AC:

116

AN:

251196

AF XY:

0.000383

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000432

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000694

AC:

1015

AN:

1461576

Hom.:

Cov.:

AF XY:

0.000710

AC XY:

516

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33476

American (AMR)

AF:

0.00161

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.0000936

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5542

European-Non Finnish (NFE)

AF:

0.000805

AC:

895

AN:

1111996

Other (OTH)

AF:

0.000530

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

136

205

273

341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000676

AC:

103

AN:

152302

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41572

American (AMR)

AF:

0.00216

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000617

AC:

AN:

68032

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000588

Hom.:

Bravo

AF:

0.000774

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000379

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

APBA2-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.3

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.091

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.13

M_CAP

Benign

0.016

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

PhyloP100

-0.21

PrimateAI

Benign

0.30

PROVEAN

Benign

0.22

REVEL

Benign

0.047

Sift

Benign

0.19

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.043

MVP

0.34

MPC

0.41

ClinPred

0.0040

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.021

gMVP

0.052

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over