19-7642116-G-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006949.4(STXBP2):c.661G>T(p.Glu221*) variant causes a stop gained, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_006949.4 stop_gained, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STXBP2 | ENST00000221283.10 | c.661G>T | p.Glu221* | stop_gained, splice_region_variant | Exon 8 of 19 | 1 | NM_006949.4 | ENSP00000221283.4 | ||
ENSG00000268400 | ENST00000698368.1 | n.*764G>T | splice_region_variant, non_coding_transcript_exon_variant | Exon 10 of 20 | ENSP00000513686.1 | |||||
ENSG00000268400 | ENST00000698368.1 | n.*764G>T | 3_prime_UTR_variant | Exon 10 of 20 | ENSP00000513686.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 35
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Familial hemophagocytic lymphohistiocytosis 5 Pathogenic:1
This sequence change creates a premature translational stop signal (p.Glu221*) in the STXBP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in STXBP2 are known to be pathogenic (PMID: 19804848, 22451424). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with STXBP2-related conditions. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.