Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000251.3:c.366+1G>C

CA346730170

2673296 (ClinVar)

Gene: MSH2
Condition: Lynch syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: e0a3434a-b1a8-468e-8aa2-5c365c8ff8d4
Approved on: 2024-09-19
Published on: 2024-10-11

HGVS expressions

NM_000251.3:c.366+1G>C
NC_000002.12:g.47408556G>C
CM000664.2:g.47408556G>C
NC_000002.11:g.47635695G>C
CM000664.1:g.47635695G>C
NC_000002.10:g.47489199G>C
NG_007110.2:g.10433G>C
ENST00000644900.2:c.366+1G>C
ENST00000233146.7:c.366+1G>C
ENST00000543555.6:c.168+1G>C
ENST00000644092.1:c.366+1G>C
ENST00000645339.1:c.366+1G>C
ENST00000645506.1:c.366+1G>C
ENST00000646415.1:c.366+1G>C
ENST00000233146.6:c.366+1G>C
ENST00000406134.5:c.366+1G>C
ENST00000454849.5:c.168+1G>C
ENST00000543555.5:c.168+1G>C
ENST00000610696.4:c.366+1G>C
ENST00000613514.4:c.366+1G>C
ENST00000617333.3:c.366+1G>C
ENST00000617938.4:c.366+1G>C
ENST00000621359.2:c.366+1G>C
NM_000251.2:c.366+1G>C
NM_001258281.1:c.168+1G>C
More

Pathogenic

Met criteria codes 3
PVS1 PP1 PM2_Supporting
Not Met criteria codes 22
BS3 BS4 BS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS3 PS1 PS4 BA1 PP3 PP2 PM3 PM1 PM5 PM4 PM6

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MSH2 Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP
The NM_000251.3:c.366+1G>C variant is in the dinucleotide of canonical donor splice site of exon 2, and predicted by SpliceAI to cause exon 2 skipping leading to a frameshift, p.(Ala72Phefs*9) (PVS1 met). Segregation analysis of pedigree data shows odds of pathogenicity = 3.23 (Australian Colon Cancer Family Registry) (>2.08; PP1 met). The variant is absent in gnomAD v2.1, v3.1 and v4.1 (PM2_Supporting met). Therefore, this variant meets the criteria to be classified as Likely Pathogenic. (VCEP specifications version 1)
Met criteria codes
PVS1
In dinucleotide of canonical donor splice site of exon 2, and predicted to cause exon 2 skipping leading to a frameshift, p.(Ala72Phefs*9) (SpliceAI).
PP1
Segregation odds of pathogenicity >2.08 (Australian Colon Cancer Family Registry)
PM2_Supporting
Absent in gnomAD v2.1, v3.1 and v4.1
Not Met criteria codes
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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