Variant Info

Frameshift: 2-48033984-G-GGATT

Gene: MSH6

pLI: na

Haploinsufficiency: 3

cHGVS: NM_000179.2:c.4068_4069insGATT

pHGVS: NP_000170.1:p.Ile1357AspfsTer3

Exon: 10/10

Intron: -/9

OMIM ClinVar gnomAD

PVS1 Flowchart

Preliminary Decision Path: NF4
  • Nonsense or Frameshift
    • Not predict
      to undergo NMD
      • Role of region in protein
        function is unknown #1
        • LoF variants in this exon are
          frequent in the general population #2
          and/or exon is absent from
          biologically-relevant transcripts
          • Unmet
#1 Neither mutational hotspot nor functional domain is found.
#2 Maximum LOF population frequency in exon 10 of NM_000179.2 is 3.30e-02, higher than the threshold (0.1%) we pre-defined.

Disease Mechanism

Gene Disease Inheritance Clinical Validity Disease Mechanism Consideration Adjusted Strength
MSH6 Lynch syndrome Autosomal Dominant Definitive No Decrease Unmet
MSH6 hereditary breast carcinoma Autosomal Dominant Disputed Not applicable Unmet
MSH6 constitutional mismatch repair deficiency syndrome Autosomal Recessive Definitive No Decrease Unmet