chr16-81786066-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_002661.5(PLCG2):c.77C>T(p.Thr26Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000865 in 1,614,134 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T26T) has been classified as Likely benign.
Frequency
Consequence
NM_002661.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCG2 | NM_002661.5 | c.77C>T | p.Thr26Met | missense_variant | 2/33 | ENST00000564138.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCG2 | ENST00000564138.6 | c.77C>T | p.Thr26Met | missense_variant | 2/33 | 1 | NM_002661.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000585 AC: 89AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000621 AC: 155AN: 249564Hom.: 0 AF XY: 0.000702 AC XY: 95AN XY: 135392
GnomAD4 exome AF: 0.000895 AC: 1308AN: 1461818Hom.: 2 Cov.: 30 AF XY: 0.000924 AC XY: 672AN XY: 727224
GnomAD4 genome AF: 0.000584 AC: 89AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.000537 AC XY: 40AN XY: 74478
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | PLCG2: BS1, BS2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jul 31, 2017 | The p.Thr26Met variant (rs189301790) has not been reported in the scientific medical literature or gene specific variant databases. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.06 percent (identified on 170 out of 277,184 chromosomes). Threonine at codon 26 is moderately conserved considering 11 species and Chinese hamster has methionine at this position suggesting that this amino acid change may be evolutionary tolerated. Additionally, computational analyses do not agree in their assessment of the impact of the variant on the protein (PolyPhen2: benign, SIFT: damaging, and Mutation Taster: disease causing). Altogether, the clinical significance of p.Thr26Met cannot be determined with certainty. - |
Familial cold autoinflammatory syndrome 3;C3553961:Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | PLCG2 NM_002661.4 exon 2 p.Thr26Met (c.77C>T): This variant has not been reported in the literature but is present in 126/126700 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs189301790). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Familial cold autoinflammatory syndrome 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at