rs1114167454
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP3PP5
The NM_001162383.2(ARHGEF2):c.1545+1del variant causes a splice donor 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
ARHGEF2
NM_001162383.2 splice_donor
NM_001162383.2 splice_donor
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.71
Genes affected
ARHGEF2 (HGNC:682): (Rho/Rac guanine nucleotide exchange factor 2) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form complex with G proteins and stimulate rho-dependent signals. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Jun 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 1-155958318-AC-A is Pathogenic according to our data. Variant chr1-155958318-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 427795.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF2 | NM_001162383.2 | c.1545+1del | splice_donor_variant | ENST00000361247.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF2 | ENST00000361247.9 | c.1545+1del | splice_donor_variant | 1 | NM_001162383.2 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
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
Neurodevelopmental disorder with midbrain and hindbrain malformations Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 15, 2017 | - - |
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
DS_DG_spliceai
Position offset: 3
DS_DL_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at