chr9-5029884-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_004972.4(JAK2):c.328C>T(p.His110Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,611,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004972.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAK2 | NM_004972.4 | c.328C>T | p.His110Tyr | missense_variant | 4/25 | ENST00000381652.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAK2 | ENST00000381652.4 | c.328C>T | p.His110Tyr | missense_variant | 4/25 | 1 | NM_004972.4 | P1 | |
JAK2 | ENST00000636127.1 | c.328C>T | p.His110Tyr | missense_variant | 4/16 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248890Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134534
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1458920Hom.: 0 Cov.: 29 AF XY: 0.0000248 AC XY: 18AN XY: 725792
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74338
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2022 | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 110 of the JAK2 protein (p.His110Tyr). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt JAK2 protein function. This variant has not been reported in the literature in individuals affected with JAK2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at