rs2838003

Positions:

• chr21-41277430-C-A
• chr21-41277430-C-T
• chr21-41277430-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000330333.11(BACE2):​c.*1806C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: BACE2 ENST00000330333.11 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BACE2	NM_012105.5	c.*1806C>A		3_prime_UTR_variant	9/9	ENST00000330333.11	NP_036237.2
BACE2	NM_138991.3	c.*1806C>A		3_prime_UTR_variant	8/8		NP_620476.1
BACE2	NM_138992.3	c.*2003C>A		3_prime_UTR_variant	8/8		NP_620477.1
BACE2	XM_017028314.2	c.*1806C>A		3_prime_UTR_variant	10/10		XP_016883803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACE2	ENST00000330333.11	c.*1806C>A		3_prime_UTR_variant	9/9	1	NM_012105.5	ENSP00000332979	P1
BACE2	ENST00000347667.5	c.*1806C>A		3_prime_UTR_variant	8/8	1		ENSP00000327528

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.59

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;