Variant Info - hg38

Frameshift: 2-47806845-G-GGATT

Gene: MSH6

pLI: na

Haploinsufficiency: 3

cHGVS: NM_000179.3:c.4068_4069insGATT

pHGVS: NP_000170.1:p.Ile1357AspfsTer3

Exon: 10/10

Intron: -/9

OMIM ClinVar gnomAD

PVS1 Flowchart

Preliminary Decision Path: NF6
  • Nonsense or Frameshift
    • Not predict to undergo NMD
      • Role of region in protein
        function is unknown #1
        • LoF variants in this exon are
          not frequent in the general population #2 and
          exon is present in biologically-relevant transcripts
          • Variant removes <10% of protein
            • Moderate
#1 Neither mutational hotspot nor functional domain is found.
#2 No LOF variant is found or the LOF variant dosen't exist in gnomAD.

Disease Mechanism

Gene Disease Inheritance Clinical Validity Disease Mechanism Consideration Adjusted Strength
MSH6 hereditary breast carcinoma AD Disputed Not applicable Unmet
MSH6 Lynch syndrome AD Definitive No Decrease Moderate
MSH6 mismatch repair cancer syndrome 1 AR Definitive No Decrease Moderate