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KIT
Final classification
Likely Benign
KIT c.1990+8C>T · p.?
KIT

NM_000222.2:c.1990+8C>T is an intronic variant at position +8 in intron 13 of KIT, classified as Likely benign based on the generic ACMG/AMP 2015 framework (PMID:25741868).

Gene
KIT
Transcript
NM_000222.2
HGVS · transcript:coding
NM_000222.2:c.1990+8C>T
Consequence
N/A
GRCh38
chr4:54728129 C>T
GRCh37
chr4:55594295 C>T
Basis gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting benign, BP6 supporting benign; combination = 1 supporting + 2 supporting benign, which maps to Likely Benign. ▾
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting benign, BP6 supporting benign; combination = 1 supporting + 2 supporting benign, which maps to Likely Benign.
Classification rationale
PM2 BP4BP6 Likely Benign
KIT c.1990+8C>T

NM_000222.2:c.1990+8C>T is an intronic variant at position +8 in intron 13 of KIT, classified as Likely benign based on the generic ACMG/AMP 2015 framework (PMID:25741868).1 SpliceAI predicts no significant splicing impact (max delta score=0.02), meeting BP4 at supporting benign level.2 The variant is classified as Likely benign in ClinVar (VC ID 415791) by Labcorp Genetics/Invitae, meeting BP6 at supporting benign level.3 The variant is present at extremely low frequency in gnomAD (v2.1 AF=0.00279%, v4.1 AF=0.00178%), meeting PM2 at supporting pathogenic level.4 With two supporting benign criteria (BP4, BP6) and one supporting pathogenic criterion (PM2), the net evidence meets the generic ACMG/AMP threshold for Likely benign (≥2 supporting benign criteria).5

PM2 + BP4 + BP6 → Likely Benign
1 generic_acmg_combination_rules
2 spliceai ↗
3 clinvar ↗
4 gnomad_v2 ↗gnomad_v4 ↗
5 generic_acmg_combination_rules
Gene diagram · NM_000222.2 · variants mapped to exon structure
KIT NM_000222.2
Fetching transcript structure from UCSC…
Applied criteria · 3 met · select any tile
Met
Not met
Not assessed
N/A
Strength very strong supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
—
—
—
Rationale
Select a criterion.
Sources
Evidence used
    Gaps remaining
      Rule
      —
      Research & evidence
      Population frequency · supports benign
      gnomAD v4.1 screenshot
      gnomAD v4.1
      gnomAD v2.1 screenshot
      gnomAD v2.1
      v4.1
      This variant is present in gnomAD v4.1 (AF= 1.77833e-05; MAF= 0.00178%, 28/1574512 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 8.85936e-05; MAF= 0.00886%, 8/90300 alleles, homozygotes = 1); grpmax FAF= 4.401e-05.
      v2.1
      This variant is present in gnomAD v2.1 (AF= 2.79394e-05; MAF= 0.00279%, 7/250542 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 6.53381e-05; MAF= 0.00653%, 2/30610 alleles, homozygotes = 1); grpmax FAF= 1.082e-05.
      🇨🇦 CA
      Absent from gnomAD-Canada v1.0.
      Allele frequency by ancestry
      three datasets · side by side
      gnomAD v4.1
      0.0018% · 28 / 1,574,512
      1 hom · FAF 0.0044%
      South Asian
      8 / 90,300
      0.0089%
      1 hom
      Admixed American
      2 / 59,918
      0.0033%
      European (non-Finnish)
      18 / 1,144,066
      0.0016%
      + 7 not observed (Remaining individuals, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American)
      gnomAD v2.1
      0.0028% · 7 / 250,542
      1 hom · FAF 0.0011%
      South Asian
      2 / 30,610
      0.0065%
      1 hom
      Admixed American
      2 / 34,482
      0.0058%
      European (non-Finnish)
      3 / 113,108
      0.0027%
      + 5 not observed (African/African American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals)
      gnomAD Canada 🇨🇦
      Absent · 0 / ?
      0 hom
      Not observed in any ancestry group.
      gnomAD v4 ↗ gnomAD v2 ↗ gnomAD 🇨🇦 ↗
      ClinVar screenshot
      ClinVar
      This variant has been reported in ClinVar as Likely benign (1 clinical laboratory). (ClinVarID = 415791)
      ClinVar ↗
      SpliceAI screenshot
      In silico
      SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
      SpliceAI ↗
      Functional No data
      No calibrated functional assay or RNA evidence was identified for this variant.
      OncoKB ↗
      COSMIC screenshot
      COSMIC
      Somatic evidence
      COSMIC
      This variant has not previously been reported in somatic cancers (COSMIC).
      Hotspots
      This variant does not lie in a statistically significant cancer hotspot.
      COSMIC ↗
      Sources & reference links
      7Sources
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      gnomAD-Canada
      SpliceAI
      OncoKB
      COSMIC
      Triaged references · 4 PMIDs not cited in assessment
      23852704 ↗ Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update. CLINVAR
      25394175 ↗ A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. CLINVAR
      22685257 ↗ The UK NEQAS for Molecular Genetics scheme for gastrointestinal stromal tumour: findings and recommendations following four rounds of circulation. CLINVAR
      28492532 ↗ Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. CLINVAR