chr15-51965894-A-AT
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_138792.4(LEO1):c.668_669insA(p.Asp223GlufsTer2) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
LEO1
NM_138792.4 frameshift
NM_138792.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.26
Genes affected
LEO1 (HGNC:30401): (LEO1 homolog, Paf1/RNA polymerase II complex component) LEO1, parafibromin (CDC73; MIM 607393), CTR9 (MIM 609366), and PAF1 (MIM 610506) form the PAF protein complex that associates with the RNA polymerase II subunit POLR2A (MIM 180660) and with a histone methyltransferase complex (Rozenblatt-Rosen et al., 2005 [PubMed 15632063]).[supplied by OMIM, Mar 2008]
MAPK6 (HGNC:6879): (mitogen-activated protein kinase 6) The protein encoded by this gene is a member of the Ser/Thr protein kinase family, and is most closely related to mitogen-activated protein kinases (MAP kinases). MAP kinases also known as extracellular signal-regulated kinases (ERKs), are activated through protein phosphorylation cascades and act as integration points for multiple biochemical signals. This kinase is localized in the nucleus, and has been reported to be activated in fibroblasts upon treatment with serum or phorbol esters. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEO1 | NM_138792.4 | c.668_669insA | p.Asp223GlufsTer2 | frameshift_variant | 2/12 | ENST00000299601.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEO1 | ENST00000299601.10 | c.668_669insA | p.Asp223GlufsTer2 | frameshift_variant | 2/12 | 1 | NM_138792.4 | P1 | |
LEO1 | ENST00000315141.5 | c.668_669insA | p.Asp223GlufsTer2 | frameshift_variant | 2/10 | 2 | |||
MAPK6 | ENST00000560802.1 | n.178+13612dup | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
LEO1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 08, 2022 | The LEO1 c.668dupA variant is predicted to result in a frameshift and premature protein termination (p.Asp223Glufs*2). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.