chr2-39067767-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_005633.4(SOS1):c.88-14C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,609,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005633.4 splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOS1 | NM_005633.4 | c.88-14C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000402219.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOS1 | ENST00000402219.8 | c.88-14C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005633.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152034Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251080Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135840
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457658Hom.: 0 Cov.: 28 AF XY: 0.00000276 AC XY: 2AN XY: 725522
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152034Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74256
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 05, 2014 | The 88-14C>G variant in SOS1 has not been previously reported in individuals wit h clinical features of a Noonan spectrum disorder or in large population studies . This variant is located in the 3' splice region. Computational tools do not su ggest an impact to splicing, though this information is not predictive enough to rule out pathogenicity. In summary, additional information is needed to fully a ssess the clinical significance of this variant. - |
RASopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 03, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at