rs2303113

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006949.4(STXBP2):c.1696+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 1,580,132 control chromosomes in the GnomAD database, including 7,649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 1506 hom., cov: 32)

Exomes 𝑓: 0.037 ( 6143 hom. )

Consequence

STXBP2
NM_006949.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0560

Variant links:

Genes affected

STXBP2 (HGNC:11445): (syntaxin binding protein 2) This gene encodes a member of the STXBP/unc-18/SEC1 family. The encoded protein is involved in intracellular trafficking, control of SNARE (soluble NSF attachment protein receptor) complex assembly, and the release of cytotoxic granules by natural killer cells. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2013]

STXBP2 links:

ENSG00000268400 (HGNC:):

ENSG00000268400 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 19-7647531-A-G is Benign according to our data. Variant chr19-7647531-A-G is described in ClinVar as [Benign]. Clinvar id is 260099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP2	NM_006949.4 link	c.1696+20A>G		intron_variant	Intron 18 of 18	ENST00000221283.10	NP_008880.2	Q15833-1Q53GF4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP2	ENST00000221283.10 link	c.1696+20A>G		intron_variant	Intron 18 of 18	1	NM_006949.4	ENSP00000221283.4		Q15833-1
ENSG00000268400	ENST00000698368.1 link	n.*1819A>G		downstream_gene_variant				ENSP00000513686.1		A0A8V8TM65

Frequencies

GnomAD3 genomes

AF:

0.0933

AC:

14152

AN:

151726

Hom.:

1498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0364

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.0922

Gnomad FIN

AF:

0.0719

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.0717

GnomAD3 exomes

AF:

0.0834

AC:

16397

AN:

196508

Hom.:

2109

AF XY:

0.0771

AC XY:

8209

AN XY:

106442

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.100

Gnomad ASJ exome

AF:

0.0330

Gnomad EAS exome

AF:

0.479

Gnomad SAS exome

AF:

0.0737

Gnomad FIN exome

AF:

0.0653

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.0484

GnomAD4 exome

AF:

0.0369

AC:

52760

AN:

1428288

Hom.:

6143

Cov.:

AF XY:

0.0372

AC XY:

26363

AN XY:

707920

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.100

Gnomad4 ASJ exome

AF:

0.0326

Gnomad4 EAS exome

AF:

0.491

Gnomad4 SAS exome

AF:

0.0712

Gnomad4 FIN exome

AF:

0.0636

Gnomad4 NFE exome

AF:

0.00958

Gnomad4 OTH exome

AF:

0.0612

GnomAD4 genome

AF:

0.0934

AC:

14185

AN:

151844

Hom.:

1506

Cov.:

AF XY:

0.0992

AC XY:

7362

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.0364

Gnomad4 EAS

AF:

0.482

Gnomad4 SAS

AF:

0.0923

Gnomad4 FIN

AF:

0.0719

Gnomad4 NFE

AF:

0.0120

Gnomad4 OTH

AF:

0.0714

Alfa

AF:

0.0469

Hom.:

102

Bravo

AF:

0.101

Asia WGS

AF:

0.258

AC:

894

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial hemophagocytic lymphohistiocytosis 5

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.9

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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