rs1554050230
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_002890.3(RASA1):c.2707C>T(p.Arg903Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_002890.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RASA1 | NM_002890.3 | c.2707C>T | p.Arg903Ter | stop_gained | 21/25 | ENST00000274376.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RASA1 | ENST00000274376.11 | c.2707C>T | p.Arg903Ter | stop_gained | 21/25 | 1 | NM_002890.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455368Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 723894
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Capillary malformation-arteriovenous malformation syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2022 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 464861). This premature translational stop signal has been observed in individual(s) with capillary malformation-arteriovenous malformation (PMID: 24038909, 26499346). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg903*) in the RASA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RASA1 are known to be pathogenic (PMID: 24038909). - |
Capillary malformation-arteriovenous malformation 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 23, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at