Variant chr21-41243366-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_012105.5(BACE2):c.748-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,578,428 control chromosomes in the GnomAD database, including 61,160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.36 ( 13983 hom., cov: 32)

Exomes 𝑓: 0.24 ( 47177 hom. )

Consequence

BACE2
NM_012105.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001374

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.359

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 21-41243366-C-T is Benign according to our data. Variant chr21-41243366-C-T is described in ClinVar as [Benign]. Clinvar id is 3059580.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
BACE2	NM_012105.5 linkuse as main transcript	c.748-10C>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000330333.11	NP_036237.2
BACE2	NM_138991.3 linkuse as main transcript	c.748-10C>T	splice_polypyrimidine_tract_variant, intron_variant		NP_620476.1
BACE2	NM_138992.3 linkuse as main transcript	c.748-10C>T	splice_polypyrimidine_tract_variant, intron_variant		NP_620477.1
BACE2	XM_017028314.2 linkuse as main transcript	c.463-10C>T	splice_polypyrimidine_tract_variant, intron_variant		XP_016883803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACE2	ENST00000330333.11 linkuse as main transcript	c.748-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_012105.5	ENSP00000332979	P1	Q9Y5Z0-1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55071

AN:

151858

Hom.:

13951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.722

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.0720

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.338

GnomAD3 exomes

AF:

0.235

AC:

54424

AN:

231610

Hom.:

8904

AF XY:

0.228

AC XY:

28532

AN XY:

125302

show subpopulations

Gnomad AFR exome

AF:

0.731

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.273

Gnomad EAS exome

AF:

0.0602

Gnomad SAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.241

AC:

343972

AN:

1426452

Hom.:

47177

Cov.:

AF XY:

0.238

AC XY:

168736

AN XY:

707658

show subpopulations

Gnomad4 AFR exome

AF:

0.743

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.279

Gnomad4 EAS exome

AF:

0.0712

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.257

GnomAD4 genome

AF:

0.363

AC:

55148

AN:

151976

Hom.:

13983

Cov.:

AF XY:

0.354

AC XY:

26273

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.722

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.277

Gnomad4 EAS

AF:

0.0720

Gnomad4 SAS

AF:

0.193

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.338

Alfa

AF:

0.270

Hom.:

10100

Bravo

AF:

0.381

Asia WGS

AF:

0.173

AC:

604

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BACE2-related disorder

Benign:1

Benign, no assertion criteria provided

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

-0.86

CADD

Benign

3.9

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

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