rs2838003

chr21-41277430-C-Tchr21-41277430-C-Gchr21-41277430-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.962

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
BACE2	NM_012105.5	c.*1806C>T		3_prime_UTR_variant	9/9	ENST00000330333.11
BACE2	NM_138991.3	c.*1806C>T		3_prime_UTR_variant	8/8
BACE2	NM_138992.3	c.*2003C>T		3_prime_UTR_variant	8/8
BACE2	XM_017028314.2	c.*1806C>T		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BACE2	ENST00000330333.11	c.*1806C>T		3_prime_UTR_variant	9/9	1	NM_012105.5	P1
BACE2	ENST00000347667.5	c.*1806C>T		3_prime_UTR_variant	8/8	1

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107812 AN: 151902 Hom.: 38841 Cov.: 31

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: 14 AN: 16 Hom.: 6 Cov.: 0 AF XY: 0.800 AC XY: 8 AN XY: 10

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.: 31 AF XY: 0.716 AC XY: 53196 AN XY: 74344

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

Other links and lift over

dbSNP: rs2838003; hg19: chr21-42649357;