rs12898588

Variant names:

• chr15-50717059-C-T
• rs12898588
• NM_032802.4:c.1488+2881G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032802.4(SPPL2A):​c.1488+2881G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0958 in 152,228 control chromosomes in the GnomAD database, including 786 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 0.096 (786 hom., cov: 32)
• Consequence: SPPL2A NM_032802.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• Publications: 4 publications found

Genes affected

SPPL2A (HGNC:30227): (signal peptide peptidase like 2A) This gene encodes a member of the GXGD family of aspartic proteases, which are transmembrane proteins with two conserved catalytic motifs localized within the membrane-spanning regions, as well as a member of the signal peptide peptidase-like protease (SPPL) family. This protein is expressed in all major adult human tissues and localizes to late endosomal compartments and lysosomal membranes. A pseudogene of this gene also lies on chromosome 15. [provided by RefSeq, Feb 2012]

SPPL2A Gene-Disease associations (from GenCC):

• immunodeficiency 86

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPPL2A	NM_032802.4	c.1488+2881G>A		intron_variant	Intron 14 of 14	ENST00000261854.10	NP_116191.2
SPPL2A	NM_001438111.1	c.1542+2881G>A		intron_variant	Intron 15 of 15		NP_001425040.1
SPPL2A	NM_001438112.1	c.1327+5065G>A		intron_variant	Intron 13 of 13		NP_001425041.1
SPPL2A	XM_017022680.2	c.1381+5065G>A		intron_variant	Intron 14 of 14		XP_016878169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPPL2A	ENST00000261854.10	c.1488+2881G>A		intron_variant	Intron 14 of 14	1	NM_032802.4	ENSP00000261854.5

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 14561 AN: 152110 Hom.: 783 Cov.: 32

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0918

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

GnomAD4 genome AF: 0.0958 AC: 14587 AN: 152228 Hom.: 786 Cov.: 32 AF XY: 0.0961 AC XY: 7155 AN XY: 74428

African (AFR) AF: 0.0531 AC: 2206 AN: 41542

American (AMR) AF: 0.0729 AC: 1114 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3468

East Asian (EAS) AF: 0.100 AC: 518 AN: 5182

South Asian (SAS) AF: 0.148 AC: 716 AN: 4828

European-Finnish (FIN) AF: 0.119 AC: 1256 AN: 10594

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8215 AN: 68006

Other (OTH) AF: 0.0965 AC: 204 AN: 2114

Alfa AF: 0.112 Hom.: 559

Bravo AF: 0.0874

Asia WGS AF: 0.148 AC: 513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs12898588; hg19: chr15-51009256;