rs809916

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006949.4(STXBP2):c.1539-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,611,754 control chromosomes in the GnomAD database, including 45,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3599 hom., cov: 33)

Exomes 𝑓: 0.24 ( 42282 hom. )

Consequence

STXBP2
NM_006949.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.12

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

familial hemophagocytic lymphohistiocytosis 5
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
hereditary hemophagocytic lymphohistiocytosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
microvillus inclusion disease
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

STXBP2 links:

ENSG00000268400 (HGNC:):

ENSG00000268400 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 19-7647307-G-A is Benign according to our data. Variant chr19-7647307-G-A is described in ClinVar as Benign. ClinVar VariationId is 260093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006949.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STXBP2	NM_006949.4	MANE Select	c.1539-47G>A	intron	N/A	NP_008880.2
STXBP2	NM_001272034.2		c.1572-47G>A	intron	N/A	NP_001258963.1
STXBP2	NM_001127396.3		c.1530-47G>A	intron	N/A	NP_001120868.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STXBP2	ENST00000221283.10	TSL:1 MANE Select	c.1539-47G>A	intron	N/A	ENSP00000221283.4
STXBP2	ENST00000414284.6	TSL:1	c.1530-47G>A	intron	N/A	ENSP00000409471.1
STXBP2	ENST00000597068.5	TSL:1	n.*287-47G>A	intron	N/A	ENSP00000471327.1

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32481

AN:

152084

Hom.:

3594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.481

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.245

Gnomad OTH

AF:

0.210

GnomAD2 exomes

AF:

0.208

AC:

49872

AN:

239806

AF XY:

0.207

show subpopulations

Gnomad AFR exome

AF:

0.184

Gnomad AMR exome

AF:

0.189

Gnomad ASJ exome

AF:

0.205

Gnomad EAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.216

Gnomad NFE exome

AF:

0.246

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.238

AC:

346814

AN:

1459552

Hom.:

42282

Cov.:

AF XY:

0.235

AC XY:

170723

AN XY:

726110

show subpopulations

African (AFR)

AF:

0.187

AC:

6244

AN:

33472

American (AMR)

AF:

0.193

AC:

8648

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

5258

AN:

26104

East Asian (EAS)

AF:

0.125

AC:

4965

AN:

39692

South Asian (SAS)

AF:

0.149

AC:

12851

AN:

86242

European-Finnish (FIN)

AF:

0.219

AC:

11297

AN:

51542

Middle Eastern (MID)

AF:

0.198

AC:

1128

AN:

5686

European-Non Finnish (NFE)

AF:

0.254

AC:

282571

AN:

1111770

Other (OTH)

AF:

0.230

AC:

13852

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

18111

36223

54334

72446

90557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9528

19056

28584

38112

47640

<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:

0.214

AC:

32501

AN:

152202

Hom.:

3599

Cov.:

AF XY:

0.210

AC XY:

15654

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.187

AC:

7767

AN:

41532

American (AMR)

AF:

0.197

AC:

3022

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

672

AN:

3466

East Asian (EAS)

AF:

0.113

AC:

586

AN:

5166

South Asian (SAS)

AF:

0.144

AC:

698

AN:

4832

European-Finnish (FIN)

AF:

0.208

AC:

2210

AN:

10618

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.245

AC:

16619

AN:

67966

Other (OTH)

AF:

0.210

AC:

443

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1394

2787

4181

5574

6968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<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:

0.222

Hom.:

745

Bravo

AF:

0.216

Asia WGS

AF:

0.133

AC:

461

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 12, 2023

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 41% of patients studied by a panel of primary immunodeficiencies. Number of patients: 39. Only high quality variants are reported.

not provided

Benign:2

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.51

(source)

DANN

Benign

0.85

PhyloP100

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over