chr2-39007201-TA-T
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_005633.4(SOS1):c.2511-9del variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.000512 in 1,538,302 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00053 ( 0 hom. )
Consequence
SOS1
NM_005633.4 splice_polypyrimidine_tract, intron
NM_005633.4 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.13
Genes affected
SOS1 (HGNC:11187): (SOS Ras/Rac guanine nucleotide exchange factor 1) This gene encodes a protein that is a guanine nucleotide exchange factor for RAS proteins, membrane proteins that bind guanine nucleotides and participate in signal transduction pathways. GTP binding activates and GTP hydrolysis inactivates RAS proteins. The product of this gene may regulate RAS proteins by facilitating the exchange of GTP for GDP. Mutations in this gene are associated with gingival fibromatosis 1 and Noonan syndrome type 4. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 2-39007201-TA-T is Benign according to our data. Variant chr2-39007201-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 477719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000331 (50/150926) while in subpopulation AFR AF= 0.000801 (33/41180). AF 95% confidence interval is 0.000586. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 50 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOS1 | NM_005633.4 | c.2511-9del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000402219.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOS1 | ENST00000402219.8 | c.2511-9del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005633.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000332 AC: 50AN: 150812Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000531 AC: 737AN: 1387376Hom.: 0 Cov.: 24 AF XY: 0.000471 AC XY: 327AN XY: 694196
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GnomAD4 genome AF: 0.000331 AC: 50AN: 150926Hom.: 0 Cov.: 32 AF XY: 0.000244 AC XY: 18AN XY: 73712
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Noonan syndrome 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
SOS1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 10, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 16, 2021 | - - |
Fibromatosis, gingival, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Noonan syndrome and Noonan-related syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 01, 2018 | - - |
RASopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at