2-189791827-G-A
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_000534.5(PMS1):c.18G>A(p.Ala6Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
PMS1
NM_000534.5 synonymous
NM_000534.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.205
Genes affected
PMS1 (HGNC:9121): (PMS1 homolog 1, mismatch repair system component) This gene encodes a protein belonging to the DNA mismatch repair mutL/hexB family. This protein is thought to be involved in the repair of DNA mismatches, and it can form heterodimers with MLH1, a known DNA mismatch repair protein. Mutations in this gene cause hereditary nonpolyposis colorectal cancer type 3 (HNPCC3) either alone or in combination with mutations in other genes involved in the HNPCC phenotype, which is also known as Lynch syndrome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 2-189791827-G-A is Benign according to our data. Variant chr2-189791827-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3388843.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.205 with no splicing effect.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152148Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251414Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135888
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461622Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727128
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74320
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Sep 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
PMS1: BP4, BP7 -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at