21-41275894-C-G

Variant names:

• chr21-41275894-C-G
• rs12149
• NM_012105.5:c.*270C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012105.5(BACE2):​c.*270C>G 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: 32)
• Consequence: BACE2 NM_012105.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845
• Publications: 17 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACE2	NM_012105.5	c.*270C>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000330333.11	NP_036237.2
BACE2	NM_138991.3	c.*270C>G		3_prime_UTR_variant	Exon 8 of 8		NP_620476.1
BACE2	NM_138992.3	c.*467C>G		3_prime_UTR_variant	Exon 8 of 8		NP_620477.1
BACE2	XM_017028314.2	c.*270C>G		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	c.*270C>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_012105.5	ENSP00000332979.6
BACE2	ENST00000347667.5	c.*270C>G		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000327528.4
BACE2	ENST00000328735.10	c.*467C>G		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000333854.6
BACE2	ENST00000466122.5	n.1532C>G		non_coding_transcript_exon_variant	Exon 8 of 8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.1
DANN	Benign	0.42
PhyloP100		0.84

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

Other links and lift over

dbSNP: rs12149; hg19: chr21-42647821;