rs587776885
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_005475.3(SH2B3):c.603_607del(p.Arg202GlnfsTer64) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SH2B3
NM_005475.3 frameshift
NM_005475.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.54
Genes affected
SH2B3 (HGNC:29605): (SH2B adaptor protein 3) This gene encodes a member of the SH2B adaptor family of proteins, which are involved in a range of signaling activities by growth factor and cytokine receptors. The encoded protein is a key negative regulator of cytokine signaling and plays a critical role in hematopoiesis. Mutations in this gene have been associated with susceptibility to celiac disease type 13 and susceptibility to insulin-dependent diabetes mellitus. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 12-111418744-TGCTGC-T is Pathogenic according to our data. Variant chr12-111418744-TGCTGC-T is described in ClinVar as [Pathogenic]. Clinvar id is 30444.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH2B3 | NM_005475.3 | c.603_607del | p.Arg202GlnfsTer64 | frameshift_variant | 2/8 | ENST00000341259.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH2B3 | ENST00000341259.7 | c.603_607del | p.Arg202GlnfsTer64 | frameshift_variant | 2/8 | 1 | NM_005475.3 | P1 | |
SH2B3 | ENST00000550925.2 | c.409_413del | p.Arg138GlnfsTer46 | frameshift_variant | 1/2 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Primary myelofibrosis Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 12, 2010 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at