chr3-141487109-C-T
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_006506.5(RASA2):c.26C>T(p.Ala9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,408,594 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A9S) has been classified as Uncertain significance.
Frequency
Consequence
NM_006506.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RASA2 | NM_006506.5 | c.26C>T | p.Ala9Val | missense_variant | 1/24 | ENST00000286364.9 | |
RASA2 | NM_001303246.3 | c.26C>T | p.Ala9Val | missense_variant | 1/25 | ||
RASA2 | NM_001303245.3 | c.26C>T | p.Ala9Val | missense_variant | 1/24 | ||
RASA2 | XM_047448652.1 | c.26C>T | p.Ala9Val | missense_variant | 1/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RASA2 | ENST00000286364.9 | c.26C>T | p.Ala9Val | missense_variant | 1/24 | 1 | NM_006506.5 | P1 | |
RASA2 | ENST00000515549.1 | c.26C>T | p.Ala9Val | missense_variant, NMD_transcript_variant | 1/5 | 4 |
Frequencies
GnomAD3 genomes AF: 0.00416 AC: 626AN: 150486Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00405 AC: 370AN: 91248Hom.: 4 AF XY: 0.00433 AC XY: 223AN XY: 51508
GnomAD4 exome AF: 0.00616 AC: 7752AN: 1258000Hom.: 26 Cov.: 31 AF XY: 0.00602 AC XY: 3730AN XY: 620074
GnomAD4 genome AF: 0.00414 AC: 624AN: 150594Hom.: 6 Cov.: 32 AF XY: 0.00392 AC XY: 288AN XY: 73554
ClinVar
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 30, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | RASA2: BS2 - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 01, 2023 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 26, 2019 | Variant summary: RASA2 c.26C>T (p.Ala9Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0041 in 91248 control chromosomes in the gnomAD database, including 4 homozygotes. The observed variant frequency is approximately 811 fold of the estimated maximal expected allele frequency for a pathogenic variant in RASA2 causing Noonan Syndrome and Related Conditions phenotype (5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.26C>T in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 09, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
RASA2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 14, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at