Variant chr21-41168527-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_012105.5(BACE2):c.264T>A(p.Ser88=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,346,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

BACE2
NM_012105.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.71

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 -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 21-41168527-T-A is Benign according to our data. Variant chr21-41168527-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 755920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.7 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BACE2	NM_012105.5 linkuse as main transcript	c.264T>A	p.Ser88=	synonymous_variant	1/9	ENST00000330333.11
BACE2	NM_138991.3 linkuse as main transcript	c.264T>A	p.Ser88=	synonymous_variant	1/8
BACE2	NM_138992.3 linkuse as main transcript	c.264T>A	p.Ser88=	synonymous_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BACE2	ENST00000330333.11 linkuse as main transcript	c.264T>A	p.Ser88=	synonymous_variant	1/9	1	NM_012105.5	P1	Q9Y5Z0-1
BACE2	ENST00000347667.5 linkuse as main transcript	c.264T>A	p.Ser88=	synonymous_variant	1/8	1			Q9Y5Z0-2
BACE2	ENST00000328735.10 linkuse as main transcript	c.264T>A	p.Ser88=	synonymous_variant	1/8	1			Q9Y5Z0-3

Frequencies

GnomAD3 genomes

AF:

0.000198

AC:

AN:

151822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000129

AC:

AN:

108848

Hom.:

AF XY:

0.0000498

AC XY:

AN XY:

60250

show subpopulations

Gnomad AFR exome

AF:

0.000519

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000174

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000283

AC:

338

AN:

1194944

Hom.:

Cov.:

AF XY:

0.000272

AC XY:

157

AN XY:

577910

show subpopulations

Gnomad4 AFR exome

AF:

0.0000798

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000339

Gnomad4 OTH exome

AF:

0.000126

GnomAD4 genome

AF:

0.000198

AC:

AN:

151822

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.000238

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

BACE2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 03, 2019

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

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.3

DANN

Benign

0.83

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