rs587782056
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM1PM4_Supporting
The NM_000455.5(STK11):c.250_252del(p.Lys84del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,486 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. K81K) has been classified as Likely benign.
Frequency
Consequence
NM_000455.5 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STK11 | NM_000455.5 | c.250_252del | p.Lys84del | inframe_deletion | 1/10 | ENST00000326873.12 | |
STK11 | NM_001407255.1 | c.250_252del | p.Lys84del | inframe_deletion | 1/9 | ||
STK11 | NR_176325.1 | n.1386_1388del | non_coding_transcript_exon_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STK11 | ENST00000326873.12 | c.250_252del | p.Lys84del | inframe_deletion | 1/10 | 1 | NM_000455.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000410 AC: 1AN: 243760Hom.: 0 AF XY: 0.00000753 AC XY: 1AN XY: 132808
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460344Hom.: 0 AF XY: 0.00000551 AC XY: 4AN XY: 726334
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74308
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Oct 14, 2019 | This variant causes an in-frame deletion of one amino acid at codon 84 in the STK11 protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported as a germline mutation in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/243760 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2022 | The c.250_252delAAG variant (also known as p.K84del) is located in coding exon 1 of the STK11 gene. This variant results from an in-frame AAG deletion at nucleotide positions 250 to 252. This results in the in-frame deletion of a lysine at codon 84. The deleted amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Peutz-Jeghers syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2023 | This variant, c.250_252del, results in the deletion of 1 amino acid(s) of the STK11 protein (p.Lys84del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 141849). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Melanoma, cutaneous malignant, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | May 05, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at