rs121917757
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 8P and 6B. PVS1BP6_ModerateBS2
The ENST00000311189.8(HRAS):c.64C>T(p.Gln22Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,360 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 Likely benign (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
HRAS
ENST00000311189.8 stop_gained
ENST00000311189.8 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 7.94
Genes affected
HRAS (HGNC:5173): (HRas proto-oncogene, GTPase) This gene belongs to the Ras oncogene family, whose members are related to the transforming genes of mammalian sarcoma retroviruses. The products encoded by these genes function in signal transduction pathways. These proteins can bind GTP and GDP, and they have intrinsic GTPase activity. This protein undergoes a continuous cycle of de- and re-palmitoylation, which regulates its rapid exchange between the plasma membrane and the Golgi apparatus. Mutations in this gene cause Costello syndrome, a disease characterized by increased growth at the prenatal stage, growth deficiency at the postnatal stage, predisposition to tumor formation, cognitive disability, skin and musculoskeletal abnormalities, distinctive facial appearance and cardiovascular abnormalities. Defects in this gene are implicated in a variety of cancers, including bladder cancer, follicular thyroid cancer, and oral squamous cell carcinoma. Multiple transcript variants, which encode different isoforms, have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 40 pathogenic variants in the truncated region.
BP6
Variant 11-534259-G-A is Benign according to our data. Variant chr11-534259-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 279996.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HRAS | NM_005343.4 | c.64C>T | p.Gln22Ter | stop_gained | 2/6 | ENST00000311189.8 | NP_005334.1 | |
HRAS | NM_176795.5 | c.64C>T | p.Gln22Ter | stop_gained | 2/6 | ENST00000417302.7 | NP_789765.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HRAS | ENST00000311189.8 | c.64C>T | p.Gln22Ter | stop_gained | 2/6 | 1 | NM_005343.4 | ENSP00000309845 | P1 | |
HRAS | ENST00000417302.7 | c.64C>T | p.Gln22Ter | stop_gained | 2/6 | 5 | NM_176795.5 | ENSP00000388246 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
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34
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250698Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135776
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461360Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727016
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GnomAD4 genome Cov.: 34
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34
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 30, 2019 | Predicted loss-of-function variant in a gene for which the disease mechanism is known to be gain-of-function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A;A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at