Variant chr21-41168374-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_012105.5(BACE2):c.111G>A(p.Ala37=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000686 in 1,398,120 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

BACE2
NM_012105.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0390

Variant links:

Genes affected

BACE2 (HGNC:934): (beta-secretase 2) This gene encodes an integral membrane glycoprotein that functions as an aspartic protease. The encoded protein cleaves amyloid precursor protein into amyloid beta peptide, which is a critical step in the etiology of Alzheimer's disease and Down syndrome. The protein precursor is further processed into an active mature peptide. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

BACE2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 21-41168374-G-A is Benign according to our data. Variant chr21-41168374-G-A is described in ClinVar as [Benign]. Clinvar id is 3048890.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.039 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BACE2	NM_012105.5 linkuse as main transcript	c.111G>A	p.Ala37=	synonymous_variant	1/9	ENST00000330333.11
BACE2	NM_138991.3 linkuse as main transcript	c.111G>A	p.Ala37=	synonymous_variant	1/8
BACE2	NM_138992.3 linkuse as main transcript	c.111G>A	p.Ala37=	synonymous_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BACE2	ENST00000330333.11 linkuse as main transcript	c.111G>A	p.Ala37=	synonymous_variant	1/9	1	NM_012105.5	P1	Q9Y5Z0-1
BACE2	ENST00000347667.5 linkuse as main transcript	c.111G>A	p.Ala37=	synonymous_variant	1/8	1			Q9Y5Z0-2
BACE2	ENST00000328735.10 linkuse as main transcript	c.111G>A	p.Ala37=	synonymous_variant	1/8	1			Q9Y5Z0-3

Frequencies

GnomAD3 genomes

AF:

0.00310

AC:

469

AN:

151472

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000789

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00137

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000193

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.000277

AC:

AN:

54144

Hom.:

AF XY:

0.000284

AC XY:

AN XY:

31660

show subpopulations

Gnomad AFR exome

AF:

0.00909

Gnomad AMR exome

AF:

0.000753

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000191

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000393

AC:

490

AN:

1246542

Hom.:

Cov.:

AF XY:

0.000381

AC XY:

233

AN XY:

611808

show subpopulations

Gnomad4 AFR exome

AF:

0.00888

Gnomad4 AMR exome

AF:

0.000720

Gnomad4 ASJ exome

AF:

0.0000508

Gnomad4 EAS exome

AF:

0.000110

Gnomad4 SAS exome

AF:

0.000367

Gnomad4 FIN exome

AF:

0.0000471

Gnomad4 NFE exome

AF:

0.000185

Gnomad4 OTH exome

AF:

0.000897

GnomAD4 genome

AF:

0.00309

AC:

469

AN:

151578

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

221

AN XY:

74050

show subpopulations

Gnomad4 AFR

AF:

0.0104

Gnomad4 AMR

AF:

0.000788

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00137

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.000193

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00270

Hom.:

Asia WGS

AF:

0.00116

AC:

AN:

3452

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

BACE2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 02, 2020

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

-0.74

CADD

Benign

7.6

DANN

Benign

0.96

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