19-7647539-G-A

Variant names:

• chr19-7647539-G-A
• rs34976997
• NM_006949.4:c.1696+28G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006949.4(STXBP2):​c.1696+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000492 in 1,422,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: STXBP2 NM_006949.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63
• Publications: 10 publications found

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: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, PanelApp Australia, 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

ENSG00000268400 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP2	NM_006949.4	MANE Select	c.1696+28G>A		intron	N/A	NP_008880.2	Q15833-1
	STXBP2	NM_001272034.2		c.1729+28G>A		intron	N/A	NP_001258963.1	Q15833-3
	STXBP2	NM_001127396.3		c.1687+28G>A		intron	N/A	NP_001120868.1	Q15833-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP2	ENST00000221283.10	TSL:1 MANE Select	c.1696+28G>A		intron	N/A	ENSP00000221283.4	Q15833-1
	STXBP2	ENST00000414284.6	TSL:1	c.1687+28G>A		intron	N/A	ENSP00000409471.1	Q15833-2
	STXBP2	ENST00000597068.5	TSL:1	n.*444+28G>A		intron	N/A	ENSP00000471327.1	M0R0M7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000260 AC: 5 AN: 192400 AF XY: 0.0000192

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000369

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000492 AC: 7 AN: 1422396 Hom.: 0 Cov.: 50 AF XY: 0.00000426 AC XY: 3 AN XY: 704428

African (AFR) AF: 0.00 AC: 0 AN: 32084

American (AMR) AF: 0.00 AC: 0 AN: 38710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25288

East Asian (EAS) AF: 0.000189 AC: 7 AN: 37022

South Asian (SAS) AF: 0.00 AC: 0 AN: 83118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5528

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090892

Other (OTH) AF: 0.00 AC: 0 AN: 58738

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 776

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.4
DANN	Benign	0.75
PhyloP100		2.6
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0

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

Other links and lift over

dbSNP: rs34976997; hg19: chr19-7712425;