19-7646335-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006949.4(STXBP2):c.1443T>C(p.Asp481Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,605,256 control chromosomes in the GnomAD database, including 125,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14749 hom., cov: 32)

Exomes 𝑓: 0.38 ( 111175 hom. )

Consequence

STXBP2
NM_006949.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: -1.00

Publications

26 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 19-7646335-T-C is Benign according to our data. Variant chr19-7646335-T-C is described in ClinVar as Benign. ClinVar VariationId is 260089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP2	NM_006949.4 link	c.1443T>C	p.Asp481Asp	synonymous_variant	Exon 16 of 19	ENST00000221283.10	NP_008880.2	Q15833-1Q53GF4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STXBP2	ENST00000221283.10 link	c.1443T>C	p.Asp481Asp	synonymous_variant	Exon 16 of 19	1	NM_006949.4	ENSP00000221283.4	Q15833-1
ENSG00000268400	ENST00000698368.1 link	n.*1546T>C		non_coding_transcript_exon_variant	Exon 18 of 20			ENSP00000513686.1	A0A8V8TM65
ENSG00000268400	ENST00000698368.1 link	n.*1546T>C		3_prime_UTR_variant	Exon 18 of 20			ENSP00000513686.1	A0A8V8TM65

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65729

AN:

151924

Hom.:

14720

Cov.:

show subpopulations

Gnomad AFR

AF:

0.496

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.464

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.704

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.527

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.414

GnomAD2 exomes

AF:

0.418

AC:

97048

AN:

232440

AF XY:

0.408

show subpopulations

Gnomad AFR exome

AF:

0.499

Gnomad AMR exome

AF:

0.454

Gnomad ASJ exome

AF:

0.303

Gnomad EAS exome

AF:

0.683

Gnomad FIN exome

AF:

0.509

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.401

GnomAD4 exome

AF:

0.385

AC:

558921

AN:

1453214

Hom.:

111175

Cov.:

AF XY:

0.383

AC XY:

276300

AN XY:

722094

show subpopulations

African (AFR)

AF:

0.504

AC:

16837

AN:

33426

American (AMR)

AF:

0.455

AC:

19509

AN:

42888

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

7948

AN:

25936

East Asian (EAS)

AF:

0.720

AC:

28316

AN:

39342

South Asian (SAS)

AF:

0.342

AC:

28962

AN:

84714

European-Finnish (FIN)

AF:

0.502

AC:

26389

AN:

52608

Middle Eastern (MID)

AF:

0.325

AC:

1866

AN:

5750

European-Non Finnish (NFE)

AF:

0.366

AC:

405232

AN:

1108428

Other (OTH)

AF:

0.397

AC:

23862

AN:

60122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

18542

37084

55626

74168

92710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13016

26032

39048

52064

65080

<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:

0.433

AC:

65815

AN:

152042

Hom.:

14749

Cov.:

AF XY:

0.440

AC XY:

32696

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.496

AC:

20575

AN:

41468

American (AMR)

AF:

0.464

AC:

7093

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

1076

AN:

3468

East Asian (EAS)

AF:

0.703

AC:

3630

AN:

5162

South Asian (SAS)

AF:

0.361

AC:

1738

AN:

4818

European-Finnish (FIN)

AF:

0.527

AC:

5577

AN:

10590

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.367

AC:

24949

AN:

67948

Other (OTH)

AF:

0.418

AC:

882

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1930

3860

5790

7720

9650

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<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:

0.384

Hom.:

6884

Bravo

AF:

0.432

Asia WGS

AF:

0.529

AC:

1839

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 71% of patients studied by a panel of primary immunodeficiencies. Number of patients: 68. Only high quality variants are reported. -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Nov 12, 2018

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

- -

Familial hemophagocytic lymphohistiocytosis 5

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial hemophagocytic lymphohistiocytosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

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

-0.72

CADD

Benign

0.11

(source)

DANN

Benign

0.47

PhyloP100

-1.0

PromoterAI

0.15

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over