Table 1 PMS2 variants analyzed in this study, gnomAD information and patient-related data.

From: Analysis of structure and conservation for supporting functional evaluation of PMS2 missense variants

PMS2 variant

Patient-related data

Further information (previous publications)

ACMG classifi-cation based on clinical data

Protein change/Nucleotide change/SNP identifier/gnomAD v4.1.0 Grpmax filtering allele frequency (corresponding ACMG criteria) and number of homozygotes

Identifier

Country

Gen-der

Carcinoma disease(s) (age at diagnosis in years)

Family data/criteria

MSI

IHC3

Further data 1

p.Asp286Gly c.857A>G rs116788608 0.000124 (BS1) Homozygotes: 0

286-ARG-1

Argentina

m

CRC (40)

Bethesda

 

++00

MLPA: normal

 

BP5

286-ARG-2

Argentina

f

Stomach (37); CRC (47)

Amsterdam I

 

///0

  

286-BRA-1

Brazil

m

Liposarcoma (38)

Not specific

  

Additional VUS (126 genes tested): WT1: c.1048 T > C; p.Cys350Arg

 

286-BRA-2=CM316

Brazil

f

Breast (39)

NCCN 2

  

BRCA1/2: no mutations. MLPA in BRCA1/2 normal

 

Li-14

France

 

CRC (42)

 

MSS

++++

One first degree relative with ovarian cancer (54 y); two distant relatives with CRC < 50 years.

See (Wang et al. 2020)

503989-623

France

       

p.Asn335Ser c.1004A>G rs200513014 0.0002997 (BS1) Homozygotes: 0

335-URU-1

Uruguay

f

Colorectal adenoma (27); polyps in endometrium and ovary (22)

NCCN 2

  

MLH1, MSH2, MSH6, MUTYH, PMS1: no mutations

 

PP4_moderate

335-BRA-1

Brazil

f

Ovarian germ cell (29); CRC (36)

Bethesda

 

//00

Additional pathogenic variant: MLH1 c.2004delA; p.Glu669Lysfs*114.

Identified in 0.2% of index cases with HBOC2 syndrome in France

335-BRA-2=CM047

Brazil

f

Breast (42) Ovary (45)

NCCN 2

  

Additional pathogenic variant: BRCA1: c.5074+2 T > C. CHEK2: c.157 T > A. (VUS); MLPA in BRCA1/2 normal

335-ARG-1

Argentina

f

Ovary (39)

NCCN 2

  

MLPA: normal

Ro-23

France

 

Duodenal cancer (43)

   

First-degree relative with CRC (45)

See (Wang et al. 2020)

Ro-25

France

 

CRC (48)

  

+++/

First-degree relative with CRC (54)

Ro-30

France

 

CRC (61)

 

MSI-H

++00

 

Ro-93

France

 

CRC (42)

  

+++0

 

Ly-02

France

 

CRC (26)

 

MSI-H

+++0

 

p.Ile679Thr c.2036T>C rs778251286 0.00000513 (PM2_supp) Homozygotes: 0

679-BRA-1

Brazil

f

CRC (50)

Bethesda

4

++++

No affected relatives

 

Reach no criteria

p.Arg799Trp c.2395C>T rs149202766 0.004805 (BA1) Homozygotes : 12

799-CRI-1

Costa Rica

f

Endometrium (31)

no cancer history in family

 

///0

  

PP4_supp

799-COL-1

Colombia

f

Ovary (72)

NCCN (HBOC)2

  

BRCA1/2, MLH1, MHS2, MSH6: no pathogenic variants

 

799-COL-2

Colombia

f

Ovary (73)

NCCN (HBOC)2

  

BRCA1/2, MLH1, MHS2, MSH6: no pathogenic variants

 

799-COL-3

Colombia

f

Breast ductal (22)

NCCN (HBOC)2

  

BRCA1/2, MLH1, MHS2, MSH6: no pathogenic variants

 

799-COL-4

Colombia

f

Ovary (31)

NCCN (HBOC)2

  

BRCA1/2, MLH1, MHS2, MSH6: no pathogenic variants

 

799-COL-5

Colombia

f

Breast ductal infiltrating (35)

NCCN (HBOC)2

  

BRCA1/2, MLH1, MHS2, MSH6: no pathogenic variants

 

734388-623

France

f

      
  1. Variant descriptions confer to HGVS format and refer to the PMS2 reference cDNA (NM_000535.7) or protein (NP_000526.2) sequences and have been checked using Mutalyzer Name Checker. 1 Except otherwise stated, no other variants have been identified in MMR genes in these patients by sequencing. 2 NCCN: National Comprehensive Cancer Network Guidelines; HBOC: Hereditary breast and ovary cancer. 3 Immunohistochemical protein expression for MSH2-MSH6-MLH1-PMS2; +: normal expression; 0: no expression; /: not tested or not conclusive. n.a. not applicable.
Back to article page