Variant chr21-41250859-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_012105.5(BACE2):c.1092C>T(p.Asp364=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,613,088 control chromosomes in the GnomAD database, including 140,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.34 ( 10798 hom., cov: 32)

Exomes 𝑓: 0.41 ( 129602 hom. )

Consequence

BACE2
NM_012105.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.23

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 21-41250859-C-T is Benign according to our data. Variant chr21-41250859-C-T is described in ClinVar as [Benign]. Clinvar id is 3060688.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BACE2	NM_012105.5 linkuse as main transcript	c.1092C>T	p.Asp364=	synonymous_variant	7/9	ENST00000330333.11
BACE2	NM_138992.3 linkuse as main transcript	c.1092C>T	p.Asp364=	synonymous_variant	7/8
BACE2	XM_017028314.2 linkuse as main transcript	c.807C>T	p.Asp269=	synonymous_variant	8/10
BACE2	NM_138991.3 linkuse as main transcript	c.984+4796C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BACE2	ENST00000330333.11 linkuse as main transcript	c.1092C>T	p.Asp364=	synonymous_variant	7/9	1	NM_012105.5	P1	Q9Y5Z0-1

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52131

AN:

151974

Hom.:

10794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.702

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.382

GnomAD3 exomes

AF:

0.451

AC:

113307

AN:

251230

Hom.:

27954

AF XY:

0.455

AC XY:

61755

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.615

Gnomad ASJ exome

AF:

0.397

Gnomad EAS exome

AF:

0.700

Gnomad SAS exome

AF:

0.553

Gnomad FIN exome

AF:

0.402

Gnomad NFE exome

AF:

0.395

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.411

AC:

600851

AN:

1460996

Hom.:

129602

Cov.:

AF XY:

0.415

AC XY:

301943

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.601

Gnomad4 ASJ exome

AF:

0.394

Gnomad4 EAS exome

AF:

0.721

Gnomad4 SAS exome

AF:

0.549

Gnomad4 FIN exome

AF:

0.402

Gnomad4 NFE exome

AF:

0.391

Gnomad4 OTH exome

AF:

0.415

GnomAD4 genome

AF:

0.343

AC:

52134

AN:

152092

Hom.:

10798

Cov.:

AF XY:

0.352

AC XY:

26156

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.486

Gnomad4 ASJ

AF:

0.402

Gnomad4 EAS

AF:

0.701

Gnomad4 SAS

AF:

0.545

Gnomad4 FIN

AF:

0.403

Gnomad4 NFE

AF:

0.388

Gnomad4 OTH

AF:

0.385

Alfa

AF:

0.387

Hom.:

27261

Bravo

AF:

0.343

Asia WGS

AF:

0.597

AC:

2073

AN:

3478

EpiCase

AF:

0.398

EpiControl

AF:

0.399

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

Oct 30, 2019

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

-0.67

CADD

Benign

2.9

DANN

Benign

0.88

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