Starting

Initialising…

KLLN

Final classification

VUS

KLLN c.-694T>G · p.?

KLLN

The KLLN c.-694T>G (NP_001119521.1:p.?) variant has not been reported in ClinVar.

Gene

KLLN

Transcript

NM_001126049.2

HGVS · transcript:coding

NM_001126049.2:c.-694T>G

Consequence

N/A

GRCh38

chr10:87863181 A>C

GRCh37

chr10:89622938 A>C

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; combination = 1 supporting, which maps to VUS. ▾

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; combination = 1 supporting, which maps to VUS.

Classification rationale

PM2 VUS

KLLN c.-694T>G

The KLLN c.-694T>G (NP_001119521.1:p.?) variant has not been reported in ClinVar.¹ This variant is absent from gnomAD v2.1 and is present at very low frequency in gnomAD v4.1 (2/185458 alleles; AF 0.00108%; highest observed population AF 0.00787% in Finnish), supporting rarity and meeting PM2 at supporting strength while remaining far below benign frequency thresholds.² SpliceAI predicts no significant splice impact for this variant (max delta score 0.08), but no validated computational evidence was identified to determine whether this upstream change has a damaging or benign regulatory effect.³

PM2 → VUS

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗

3 spliceai ↗

Gene diagram · NM_001126049.2 · variants mapped to exon structure

KLLN NM_001126049.2

Fetching transcript structure from UCSC…

Applied criteria · 1 met · select any tile

Met

Not met

Not assessed

N/A

Strength very strong supporting

Pathogenic evidence

PVS

Benign evidence

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency

gnomAD v4.1

gnomAD v2.1

v4.1

This variant is present in gnomAD v4.1 (AF= 1.07841e-05; MAF= 0.00108%, 2/185458 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 7.87154e-05; MAF= 0.00787%, 2/25408 alleles, homozygotes = 0).

v2.1

Absent from gnomAD v2.1.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

0.0011% · 2 / 185,458
0 hom

European (Finnish)

2 / 25,408

0.0079%

+ 9 not observed (Remaining individuals, Admixed American, Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish))

gnomAD v2.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant is absent from ClinVar.

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.08).

SpliceAI ↗

Functional No data

No calibrated functional assay or RNA evidence was identified for this variant.

OncoKB ↗

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

6Sources

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC