Genetic Variant APBA2:p.His127His (chr15-29054265-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001353788.2(APBA2):c.381C>T(p.His127His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,614,142 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0074 ( 53 hom. )

Consequence

APBA2
NM_001353788.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.506

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-29054265-C-T is Benign according to our data. Variant chr15-29054265-C-T is described in ClinVar as [Benign]. Clinvar id is 770621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.506 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBA2	NM_001353788.2 link	c.381C>T	p.His127His	synonymous_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.381C>T	p.His127His	synonymous_variant	Exon 4 of 15		NM_001353788.2	ENSP00000507394.1		Q99767-1

Frequencies

GnomAD3 genomes

AF:

0.00740

AC:

1126

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00886

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00705

AC:

1772

AN:

251218

Hom.:

AF XY:

0.00744

AC XY:

1011

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.0108

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00447

Gnomad FIN exome

AF:

0.00129

Gnomad NFE exome

AF:

0.00859

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.00744

AC:

10878

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00753

AC XY:

5476

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.0153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00434

Gnomad4 FIN exome

AF:

0.00142

Gnomad4 NFE exome

AF:

0.00804

Gnomad4 OTH exome

AF:

0.00806

GnomAD4 genome

AF:

0.00739

AC:

1125

AN:

152284

Hom.:

Cov.:

AF XY:

0.00731

AC XY:

544

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.0166

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00887

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00748

Hom.:

Bravo

AF:

0.00851

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0106

EpiControl

AF:

0.0124

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

APBA2-related disorder

Benign:1

Feb 21, 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

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.41

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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