chr19-7637154-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006949.4(STXBP2):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,088,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A2A) has been classified as Likely benign.
Frequency
Consequence
NM_006949.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STXBP2 | NM_006949.4 | c.5C>T | p.Ala2Val | missense_variant | 1/19 | ENST00000221283.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STXBP2 | ENST00000221283.10 | c.5C>T | p.Ala2Val | missense_variant | 1/19 | 1 | NM_006949.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000184 AC: 2AN: 1088992Hom.: 0 Cov.: 31 AF XY: 0.00000194 AC XY: 1AN XY: 514414
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Familial hemophagocytic lymphohistiocytosis 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 641714). This variant has not been reported in the literature in individuals affected with STXBP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2 of the STXBP2 protein (p.Ala2Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at