chr7-5973292-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000535.7(PMS2):c.*107A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,358,150 control chromosomes in the GnomAD database, including 256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0083 ( 143 hom., cov: 20)
Exomes 𝑓: 0.00085 ( 113 hom. )
Consequence
PMS2
NM_000535.7 3_prime_UTR
NM_000535.7 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.174
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 7-5973292-T-C is Benign according to our data. Variant chr7-5973292-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 360540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-5973292-T-C is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00829 (1157/139570) while in subpopulation AFR AF= 0.0298 (1110/37242). AF 95% confidence interval is 0.0283. There are 143 homozygotes in gnomad4. There are 571 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 143 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PMS2 | NM_000535.7 | c.*107A>G | 3_prime_UTR_variant | 15/15 | ENST00000265849.12 | NP_000526.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PMS2 | ENST00000265849.12 | c.*107A>G | 3_prime_UTR_variant | 15/15 | 1 | NM_000535.7 | ENSP00000265849 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00829 AC: 1156AN: 139474Hom.: 143 Cov.: 20
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GnomAD3 exomes AF: 0.00196 AC: 439AN: 224388Hom.: 53 AF XY: 0.00157 AC XY: 192AN XY: 122154
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GnomAD4 exome AF: 0.000853 AC: 1040AN: 1218580Hom.: 113 Cov.: 22 AF XY: 0.000728 AC XY: 446AN XY: 612442
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GnomAD4 genome AF: 0.00829 AC: 1157AN: 139570Hom.: 143 Cov.: 20 AF XY: 0.00842 AC XY: 571AN XY: 67792
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Lynch syndrome 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at