About KIT
No gene-level summary was recorded for this case.
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.No gene-level summary was recorded for this case.
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
No pathogenic criterion marked as applied in the recorded assessment.
BS1 is met at strong level: allele frequency exceeds the 0.3% threshold in the European (non-Finnish) population. gnomAD v2.1 NFE AF = 0.592% and gnomAD v4.1 NFE AF = 0.654%, both substantially above the expected frequency for rare KIT-related germline disorders (familial GIST, piebaldism).
BS2 is met at strong level: 35 homozygotes are observed in gnomAD v4.1 and 2 homozygotes in gnomAD v2.1. The presence of homozygous individuals in a general population database is inconsistent with a highly penetrant dominant germline disorder such as familial GIST or piebaldism, where homozygosity would be expected to be lethal or cause severe early-onset disease.
BP4 is met at supporting level: SpliceAI predicts no splicing impact (max delta score = 0.00) for this 5'UTR variant. No other computational predictors suggest a deleterious effect. Multiple lines of computational evidence support a benign interpretation.
BP6 is met at supporting level: ClinVar reports a consensus classification of Likely benign from multiple clinical laboratories (3 Likely benign, 1 Benign, 1 Uncertain significance). Multiple independent submitters using clinical testing methodology have reached a benign or likely benign conclusion.
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BS1 strong, BS2 strong, BP4 supporting, BP6 supporting; combination = 2 strong benign + 2 supporting benign, which maps to Benign.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 8,496 / 1,613,094 alleles. Recorded AF 0.0052669. Recorded homozygote count 35.
This variant is present in gnomAD v2.1 (AF= 0.00347566; MAF= 0.34757%, 977/281098 alleles, homozygotes = 2) and has highest observed frequency in the European (non-Finnish) population (AF= 0.00592123; MAF= 0.59212%, 758/128014 alleles, homozygotes = 1); grpmax FAF= 0.00554939.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0056595559425337396, 104/18376 alleles, homozygotes = 0).
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
3 Likely benign · 1 Uncertain significance · 1 Benign. ClinVar API review status: criteria provided, conflicting classifications.
No standalone functional evidence summary is recorded in evidence_summary.functional.
This variant has previously been reported in somatic cancers (COSMIC; COSV55412424, n = 2 times).
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 4 met · 15 not met · 0 not assessed · 7 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
NM_000222.3:c.-14T>A is a 5'UTR substitution in the KIT gene, located 14 nucleotides upstream of the ATG start codon.
This variant is present at appreciable frequency in population databases: gnomAD v2.1 allele frequency 0.35% (977/281,098 alleles, 2 homozygotes) and gnomAD v4.1 allele frequency 0.53% (8,496/1,613,094 alleles, 35 homozygotes), with the highest subpopulation frequency of 0.65% in the European (non-Finnish) population (BS1).
The observation of 35 homozygous individuals in gnomAD v4.1 is incompatible with a highly penetrant dominant germline disorder such as familial GIST or piebaldism (BS2).
SpliceAI predicts no splicing impact (max delta score = 0.00); no computational evidence suggests a deleterious effect (BP4).
ClinVar classifies this variant as Likely benign based on submissions from multiple clinical laboratories; 4 of 5 submitters concluded benign or likely benign (BP6).
This variant has been reported in COSMIC (COSV55412424) in 2 somatic cancer samples, which is consistent with a benign germline variant occasionally detected in tumor sequencing.
No variant-specific functional studies, de novo occurrences, segregation data, or pathogenic assertions from reputable sources were identified for this variant.
No criteria match.
Every interpreted variant in KIT, mapped onto the exon structure of NM_000222.3. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| European (non-Finnish)7718 / 1,179,292 | 0.006528 hom |
| South Asian294 / 91,054 | 0.00326 hom |
| Remaining individuals199 / 62,466 | 0.0032 |
| Middle Eastern12 / 6,058 | 0.002 |
| Admixed American109 / 60,006 | 0.0018 |
| European (Finnish)90 / 63,908 | 0.00141 hom |
| African/African American72 / 75,000 | 0.00096 |
| Ashkenazi Jewish1 / 29,586 | 3.4e-05 |
| East Asian1 / 44,814 | 2.2e-05 |
| European (non-Finnish)758 / 128,014 | 0.00591 hom |
| Remaining individuals22 / 7,182 | 0.0031 |
| South Asian87 / 30,580 | 0.00281 hom |
| Admixed American54 / 35,354 | 0.0015 |
| European (Finnish)36 / 24,982 | 0.0014 |
| African/African American20 / 24,770 | 0.00081 |
This variant is present in gnomAD v4.1 (AF= 0.0052669; MAF= 0.52669%, 8496/1613094 alleles, homozygotes = 35) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0065446; MAF= 0.65446%, 7718/1179292 alleles, homozygotes = 28); grpmax FAF= 0.00642186.
This variant is present in gnomAD v2.1 (AF= 0.00347566; MAF= 0.34757%, 977/281098 alleles, homozygotes = 2) and has highest observed frequency in the European (non-Finnish) population (AF= 0.00592123; MAF= 0.59212%, 758/128014 alleles, homozygotes = 1); grpmax FAF= 0.00554939.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0056595559425337396, 104/18376 alleles, homozygotes = 0).
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
4 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
This variant is present in gnomAD v4.1 (AF= 0.0052669; MAF= 0.52669%, 8496/1613094 alleles, homozygotes = 35) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0065446; MAF= 0.65446%, 7718/1179292 alleles, homozygotes = 28); grpmax FAF= 0.00642186.
This variant is present in gnomAD v2.1 (AF= 0.00347566; MAF= 0.34757%, 977/281098 alleles, homozygotes = 2) and has highest observed frequency in the European (non-Finnish) population (AF= 0.00592123; MAF= 0.59212%, 758/128014 alleles, homozygotes = 1); grpmax FAF= 0.00554939.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0056595559425337396, 104/18376 alleles, homozygotes = 0).
This variant has been reported in ClinVar as Likely benign (3 clinical laboratories) and as Uncertain significance (1 clinical laboratory) and as Benign (1 clinical laboratory). (ClinVarID = 255567)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
This variant has previously been reported in somatic cancers (COSMIC; COSV55412424, n = 2 times).