rs2054247

Positions:

• chr11-130125811-G-A
• chr11-130125811-G-C

Variant summary

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

The NM_001142276.2(APLP2):​c.1091-889G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,174 control chromosomes in the GnomAD database, including 10,344 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 (10344 hom., cov: 33)
• Consequence: APLP2 NM_001142276.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39

Genes affected

APLP2 (HGNC:598): (amyloid beta precursor like protein 2) This gene encodes amyloid precursor- like protein 2 (APLP2), which is a member of the APP (amyloid precursor protein) family including APP, APLP1 and APLP2. This protein is ubiquitously expressed. It contains heparin-, copper- and zinc- binding domains at the N-terminus, BPTI/Kunitz inhibitor and E2 domains in the middle region, and transmembrane and intracellular domains at the C-terminus. This protein interacts with major histocompatibility complex (MHC) class I molecules. The synergy of this protein and the APP is required to mediate neuromuscular transmission, spatial learning and synaptic plasticity. This protein has been implicated in the pathogenesis of Alzheimer's disease. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APLP2	NM_001142276.2	c.1091-889G>A		intron_variant		ENST00000338167.10	NP_001135748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APLP2	ENST00000338167.10	c.1091-889G>A		intron_variant		1	NM_001142276.2	ENSP00000345444	A2

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37911 AN: 152056 Hom.: 10304 Cov.: 33

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.0534

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0721

Gnomad OTH AF: 0.203

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.250 AC: 38005 AN: 152174 Hom.: 10344 Cov.: 33 AF XY: 0.243 AC XY: 18088 AN XY: 74400

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0746

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.0528

Gnomad4 FIN AF: 0.0588

Gnomad4 NFE AF: 0.0721

Gnomad4 OTH AF: 0.202

Alfa AF: 0.102 Hom.: 2069

Bravo AF: 0.279

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.088
DANN	Benign	0.30

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

Other links and lift over

dbSNP: rs2054247; hg19: chr11-129995706;