Genetic Variant BACE2:c.*1806C>T (chr21-41277430-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_012105.5(BACE2):c.*1806C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 152,038 control chromosomes in the GnomAD database, including 38,868 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 0.71 ( 38862 hom., cov: 31)

Exomes 𝑓: 0.88 ( 6 hom. )

Consequence

BACE2
NM_012105.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.962

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
BACE2	NM_012105.5 link	c.*1806C>T	3_prime_UTR_variant	Exon 9 of 9	ENST00000330333.11	NP_036237.2	Q9Y5Z0-1
BACE2	NM_138991.3 link	c.*1806C>T	3_prime_UTR_variant	Exon 8 of 8		NP_620476.1	Q9Y5Z0-2
BACE2	NM_138992.3 link	c.*2003C>T	3_prime_UTR_variant	Exon 8 of 8		NP_620477.1	Q9Y5Z0-3
BACE2	XM_017028314.2 link	c.*1806C>T	3_prime_UTR_variant	Exon 10 of 10		XP_016883803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACE2	ENST00000330333.11 link	c.*1806C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_012105.5	ENSP00000332979.6		Q9Y5Z0-1
BACE2	ENST00000347667.5 link	c.*1806C>T		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000327528.4		Q9Y5Z0-2

Frequencies

GnomAD3 genomes

AF:

0.710

AC:

107812

AN:

151902

Hom.:

38841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.603

Gnomad AMI

AF:

0.693

Gnomad AMR

AF:

0.815

Gnomad ASJ

AF:

0.737

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.836

Gnomad FIN

AF:

0.677

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.724

Gnomad OTH

AF:

0.746

GnomAD4 exome

AF:

0.875

AC:

AN:

Hom.:

Cov.:

AF XY:

0.800

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.900

Gnomad4 OTH exome

AF:

0.750

GnomAD4 genome

AF:

0.710

AC:

107882

AN:

152022

Hom.:

38862

Cov.:

AF XY:

0.716

AC XY:

53196

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.602

Gnomad4 AMR

AF:

0.815

Gnomad4 ASJ

AF:

0.737

Gnomad4 EAS

AF:

0.987

Gnomad4 SAS

AF:

0.835

Gnomad4 FIN

AF:

0.677

Gnomad4 NFE

AF:

0.724

Gnomad4 OTH

AF:

0.748

Alfa

AF:

0.734

Hom.:

37698

Bravo

AF:

0.715

Asia WGS

AF:

0.901

AC:

3130

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.40

DANN

Benign

0.67

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over