rs1555386651
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_152594.3(SPRED1):c.7_20del(p.Glu3PhefsTer2) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Consequence
SPRED1
NM_152594.3 frameshift
NM_152594.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.92
Genes affected
SPRED1 (HGNC:20249): (sprouty related EVH1 domain containing 1) The protein encoded by this gene is a member of the Sprouty family of proteins and is phosphorylated by tyrosine kinase in response to several growth factors. The encoded protein can act as a homodimer or as a heterodimer with SPRED2 to regulate activation of the MAP kinase cascade. Defects in this gene are a cause of neurofibromatosis type 1-like syndrome (NFLS). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 104 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-38253190-GCGAGGAGACGGCGA-G is Pathogenic according to our data. Variant chr15-38253190-GCGAGGAGACGGCGA-G is described in ClinVar as [Pathogenic]. Clinvar id is 547789.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-38253190-GCGAGGAGACGGCGA-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPRED1 | NM_152594.3 | c.7_20del | p.Glu3PhefsTer2 | frameshift_variant | 1/7 | ENST00000299084.9 | |
SPRED1 | XM_005254202.4 | c.7_20del | p.Glu3PhefsTer2 | frameshift_variant | 1/8 | ||
SPRED1 | XM_047432199.1 | c.-157_-144del | 5_prime_UTR_variant | 1/9 | |||
SPRED1 | XM_047432200.1 | c.-121_-108del | 5_prime_UTR_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPRED1 | ENST00000299084.9 | c.7_20del | p.Glu3PhefsTer2 | frameshift_variant | 1/7 | 1 | NM_152594.3 | P1 | |
SPRED1 | ENST00000561317.1 | c.-121_-108del | 5_prime_UTR_variant | 1/6 | 4 | ||||
SPRED1 | ENST00000561205.1 | n.345_358del | non_coding_transcript_exon_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Legius syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at