Genetic Variant NM_032802.4:c.360+87A>G (chr15-50748601-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.146

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency 86
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

SPPL2A links:

ENSG00000259773 (HGNC:):

ENSG00000259773 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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

Gene	Transcript	Tags	HGVSc	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.:

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

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8420

16840

25260

33680

42100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4646

9292

13938

18584

23230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.403

AC:

61275

AN:

151954

Hom.:

12900

Cov.:

AF XY:

0.403

AC XY:

29895

AN XY:

74270

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1867

3735

5602

7470

9337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

(source)

DANN

Benign

0.51

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over