rs8035452

Variant names:

• chr15-50748601-T-C
• rs8035452
• NM_032802.4:c.360+87A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-50748601-T-C
• chr15-50748601-T-A
• chr15-50748601-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032802.4(SPPL2A):​c.360+87A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 893,232 control chromosomes in the GnomAD database, including 61,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (12900 hom., cov: 32)
  • Exomes 𝑓: 0.36 (49060 hom.)
• Consequence: SPPL2A NM_032802.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.146
• Publications: 20 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: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000259773 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-50748601-T-C is Benign according to our data. Variant chr15-50748601-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688411.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032802.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPPL2A	NM_032802.4	MANE Select	c.360+87A>G		intron	N/A	NP_116191.2
	SPPL2A	NM_001438111.1		c.360+87A>G		intron	N/A	NP_001425040.1
	SPPL2A	NM_001438112.1		c.360+87A>G		intron	N/A	NP_001425041.1	A0A8V8TLZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPPL2A	ENST00000261854.10	TSL:1 MANE Select	c.360+87A>G		intron	N/A	ENSP00000261854.5	Q8TCT8
	SPPL2A	ENST00000951698.1		c.360+87A>G		intron	N/A	ENSP00000621757.1
	SPPL2A	ENST00000951700.1		c.360+87A>G		intron	N/A	ENSP00000621759.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61197 AN: 151836 Hom.: 12870 Cov.: 32

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.359 AC: 265937 AN: 741278 Hom.: 49060 AF XY: 0.357 AC XY: 136159 AN XY: 381060

African (AFR) AF: 0.533 AC: 8467 AN: 15886

American (AMR) AF: 0.274 AC: 6200 AN: 22646

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 4039 AN: 14846

East Asian (EAS) AF: 0.568 AC: 17472 AN: 30782

South Asian (SAS) AF: 0.330 AC: 15612 AN: 47266

European-Finnish (FIN) AF: 0.349 AC: 15084 AN: 43260

Middle Eastern (MID) AF: 0.326 AC: 1219 AN: 3742

European-Non Finnish (NFE) AF: 0.351 AC: 185117 AN: 528082

Other (OTH) AF: 0.366 AC: 12727 AN: 34768

GnomAD4 genome AF: 0.403 AC: 61275 AN: 151954 Hom.: 12900 Cov.: 32 AF XY: 0.403 AC XY: 29895 AN XY: 74270

African (AFR) AF: 0.531 AC: 22001 AN: 41432

American (AMR) AF: 0.312 AC: 4742 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 977 AN: 3472

East Asian (EAS) AF: 0.575 AC: 2971 AN: 5168

South Asian (SAS) AF: 0.329 AC: 1587 AN: 4822

European-Finnish (FIN) AF: 0.344 AC: 3633 AN: 10562

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24037 AN: 67968

Other (OTH) AF: 0.396 AC: 834 AN: 2108

Alfa AF: 0.371 Hom.: 29423

Bravo AF: 0.406

Asia WGS AF: 0.456 AC: 1583 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.15
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: rs8035452; hg19: chr15-51040798; COSMIC: COSV55941258; COSMIC: COSV55941258;