rs72824905
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002661.5(PLCG2):āc.1565C>Gā(p.Pro522Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00674 in 1,613,548 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P522L) has been classified as Uncertain significance.
Frequency
Consequence
NM_002661.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCG2 | NM_002661.5 | c.1565C>G | p.Pro522Arg | missense_variant | 17/33 | ENST00000564138.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCG2 | ENST00000564138.6 | c.1565C>G | p.Pro522Arg | missense_variant | 17/33 | 1 | NM_002661.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00495 AC: 753AN: 152118Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.00518 AC: 1291AN: 249084Hom.: 6 AF XY: 0.00525 AC XY: 709AN XY: 135126
GnomAD4 exome AF: 0.00692 AC: 10118AN: 1461312Hom.: 43 Cov.: 31 AF XY: 0.00675 AC XY: 4909AN XY: 726948
GnomAD4 genome ? AF: 0.00494 AC: 752AN: 152236Hom.: 3 Cov.: 32 AF XY: 0.00439 AC XY: 327AN XY: 74420
ClinVar
Submissions by phenotype
not provided Benign:5
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 01, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | PLCG2: BP4, BS1, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jul 27, 2017 | - - |
PLCG2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 08, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Familial cold autoinflammatory syndrome 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at