Variant 15-50748601-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000261854.10(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
ENST00000261854.10 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.146

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SPPL2A	NM_032802.4 linkuse as main transcript	c.360+87A>G	intron_variant	ENST00000261854.10	NP_116191.2
SPPL2A	XM_005254722.4 linkuse as main transcript	c.360+87A>G	intron_variant		XP_005254779.1
SPPL2A	XM_017022680.2 linkuse as main transcript	c.360+87A>G	intron_variant		XP_016878169.1
SPPL2A	XM_017022681.2 linkuse as main transcript	c.360+87A>G	intron_variant		XP_016878170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPPL2A	ENST00000261854.10 linkuse as main transcript	c.360+87A>G		intron_variant		1	NM_032802.4	ENSP00000261854	P1
	ENST00000558317.1 linkuse as main transcript	n.123-1047T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61197

AN:

151836

Hom.:

12870

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.533

Gnomad4 AMR exome

AF:

0.274

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.568

Gnomad4 SAS exome

AF:

0.330

Gnomad4 FIN exome

AF:

0.349

Gnomad4 NFE exome

AF:

0.351

Gnomad4 OTH exome

AF:

0.366

GnomAD4 genome

AF:

0.403

AC:

61275

AN:

151954

Hom.:

12900

Cov.:

AF XY:

0.403

AC XY:

29895

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.531

Gnomad4 AMR

AF:

0.312

Gnomad4 ASJ

AF:

0.281

Gnomad4 EAS

AF:

0.575

Gnomad4 SAS

AF:

0.329

Gnomad4 FIN

AF:

0.344

Gnomad4 NFE

AF:

0.354

Gnomad4 OTH

AF:

0.396

Alfa

AF:

0.360

Hom.:

15984

Bravo

AF:

0.406

Asia WGS

AF:

0.456

AC:

1583

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

DANN

Benign

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over