rs1554306440
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP3
The NM_000535.7(PMS2):โc.78_107delโ(p.Cys27_Ser36del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (โ ).
Frequency
Genomes: not found (cov: 32)
Exomes ๐: 0.0000096 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PMS2
NM_000535.7 inframe_deletion
NM_000535.7 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.91
Genes affected
PMS2 (HGNC:9122): (PMS1 homolog 2, mismatch repair system component) The protein encoded by this gene is a key component of the mismatch repair system that functions to correct DNA mismatches and small insertions and deletions that can occur during DNA replication and homologous recombination. This protein forms heterodimers with the gene product of the mutL homolog 1 (MLH1) gene to form the MutL-alpha heterodimer. The MutL-alpha heterodimer possesses an endonucleolytic activity that is activated following recognition of mismatches and insertion/deletion loops by the MutS-alpha and MutS-beta heterodimers, and is necessary for removal of the mismatched DNA. There is a DQHA(X)2E(X)4E motif found at the C-terminus of the protein encoded by this gene that forms part of the active site of the nuclease. Mutations in this gene have been associated with hereditary nonpolyposis colorectal cancer (HNPCC; also known as Lynch syndrome) and Turcot syndrome. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000535.7.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMS2 | NM_000535.7 | c.78_107del | p.Cys27_Ser36del | inframe_deletion | 2/15 | ENST00000265849.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMS2 | ENST00000265849.12 | c.78_107del | p.Cys27_Ser36del | inframe_deletion | 2/15 | 1 | NM_000535.7 | P3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000960 AC: 14AN: 1458554Hom.: 0 AF XY: 0.00000689 AC XY: 5AN XY: 725602
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
14
AN:
1458554
Hom.:
AF XY:
AC XY:
5
AN XY:
725602
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Oct 02, 2017 | - - |
Computational scores
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Name
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at