12-25209828-T-TTTC
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP3
The NM_004985.5(KRAS):c.533_534insGAA(p.Lys179dup) variant causes a inframe insertion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
KRAS
NM_004985.5 inframe_insertion
NM_004985.5 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.63
Genes affected
KRAS (HGNC:6407): (KRAS proto-oncogene, GTPase) This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
In a chain GTPase KRas (size 185) in uniprot entity RASK_HUMAN there are 120 pathogenic changes around while only 1 benign (99%) in NM_004985.5
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_004985.5. Strenght limited to Supporting due to length of the change: 1aa.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRAS | NM_004985.5 | c.533_534insGAA | p.Lys179dup | inframe_insertion | 5/5 | ENST00000311936.8 | |
KRAS | NM_033360.4 | c.*87_*88insGAA | 3_prime_UTR_variant | 6/6 | ENST00000256078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRAS | ENST00000311936.8 | c.533_534insGAA | p.Lys179dup | inframe_insertion | 5/5 | 1 | NM_004985.5 | P4 | |
KRAS | ENST00000256078.10 | c.*87_*88insGAA | 3_prime_UTR_variant | 6/6 | 1 | NM_033360.4 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Primary familial hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Blueprint Genetics | Dec 20, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at