Variant 19-7647699-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006949.4(STXBP2):c.1697-26T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 1,612,724 control chromosomes in the GnomAD database, including 323,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.67 ( 34672 hom., cov: 30)

Exomes 𝑓: 0.63 ( 288960 hom. )

Consequence

STXBP2
NM_006949.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.33

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:

STXBP2 (HGNC:):

STXBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-7647699-T-G is Benign according to our data. Variant chr19-7647699-T-G is described in ClinVar as [Benign]. Clinvar id is 260102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP2	NM_006949.4 linkuse as main transcript	c.1697-26T>G		intron_variant		ENST00000221283.10	NP_008880.2	Q15833-1Q53GF4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP2	ENST00000221283.10 linkuse as main transcript	c.1697-26T>G		intron_variant		1	NM_006949.4	ENSP00000221283.4		Q15833-1

Frequencies

GnomAD3 genomes

AF:

0.670

AC:

101634

AN:

151690

Hom.:

34624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.762

Gnomad AMI

AF:

0.691

Gnomad AMR

AF:

0.674

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.827

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.735

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.647

GnomAD3 exomes

AF:

0.635

AC:

158882

AN:

250264

Hom.:

51529

AF XY:

0.623

AC XY:

84260

AN XY:

135324

show subpopulations

Gnomad AFR exome

AF:

0.767

Gnomad AMR exome

AF:

0.649

Gnomad ASJ exome

AF:

0.509

Gnomad EAS exome

AF:

0.820

Gnomad SAS exome

AF:

0.494

Gnomad FIN exome

AF:

0.728

Gnomad NFE exome

AF:

0.613

Gnomad OTH exome

AF:

0.634

GnomAD4 exome

AF:

0.625

AC:

913664

AN:

1460916

Hom.:

288960

Cov.:

AF XY:

0.621

AC XY:

451021

AN XY:

726734

show subpopulations

Gnomad4 AFR exome

AF:

0.774

Gnomad4 AMR exome

AF:

0.656

Gnomad4 ASJ exome

AF:

0.508

Gnomad4 EAS exome

AF:

0.853

Gnomad4 SAS exome

AF:

0.492

Gnomad4 FIN exome

AF:

0.722

Gnomad4 NFE exome

AF:

0.620

Gnomad4 OTH exome

AF:

0.633

GnomAD4 genome

AF:

0.670

AC:

101744

AN:

151808

Hom.:

34672

Cov.:

AF XY:

0.674

AC XY:

49970

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.763

Gnomad4 AMR

AF:

0.674

Gnomad4 ASJ

AF:

0.505

Gnomad4 EAS

AF:

0.826

Gnomad4 SAS

AF:

0.506

Gnomad4 FIN

AF:

0.735

Gnomad4 NFE

AF:

0.612

Gnomad4 OTH

AF:

0.649

Alfa

AF:

0.554

Hom.:

3128

Bravo

AF:

0.677

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 89% of patients studied by a panel of primary immunodeficiencies. Number of patients: 85. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Familial hemophagocytic lymphohistiocytosis 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.054

DANN

Benign

0.35

BranchPoint Hunter

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

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