rs2837990

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012105.5(BACE2):​c.984+2159G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,096 control chromosomes in the GnomAD database, including 5,269 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5269 hom., cov: 32)

Consequence

BACE2
NM_012105.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.65
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BACE2NM_012105.5 linkuse as main transcriptc.984+2159G>A intron_variant ENST00000330333.11
BACE2NM_138991.3 linkuse as main transcriptc.984+2159G>A intron_variant
BACE2NM_138992.3 linkuse as main transcriptc.984+2159G>A intron_variant
BACE2XM_017028314.2 linkuse as main transcriptc.699+2159G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BACE2ENST00000330333.11 linkuse as main transcriptc.984+2159G>A intron_variant 1 NM_012105.5 P1Q9Y5Z0-1

Frequencies

GnomAD3 genomes
AF:
0.247
AC:
37585
AN:
151978
Hom.:
5259
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.387
Gnomad AMI
AF:
0.127
Gnomad AMR
AF:
0.241
Gnomad ASJ
AF:
0.237
Gnomad EAS
AF:
0.178
Gnomad SAS
AF:
0.258
Gnomad FIN
AF:
0.142
Gnomad MID
AF:
0.252
Gnomad NFE
AF:
0.187
Gnomad OTH
AF:
0.243
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.248
AC:
37648
AN:
152096
Hom.:
5269
Cov.:
32
AF XY:
0.246
AC XY:
18255
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.387
Gnomad4 AMR
AF:
0.241
Gnomad4 ASJ
AF:
0.237
Gnomad4 EAS
AF:
0.179
Gnomad4 SAS
AF:
0.257
Gnomad4 FIN
AF:
0.142
Gnomad4 NFE
AF:
0.187
Gnomad4 OTH
AF:
0.245
Alfa
AF:
0.201
Hom.:
6540
Bravo
AF:
0.258
Asia WGS
AF:
0.241
AC:
842
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.31
DANN
Benign
0.67

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.

Other links and lift over

dbSNP: rs2837990; hg19: chr21-42620149; API