NM_002661.5:c.647C>A
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_002661.5(PLCG2):c.647C>A(p.Ser216*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S216S) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_002661.5 stop_gained, splice_region
Scores
Clinical Significance
Conservation
Publications
- autoinflammation-PLCG2-associated antibody deficiency-immune dysregulationInheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
- familial cold autoinflammatory syndrome 3Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
Genome browser will be placed here
ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLCG2 | NM_002661.5 | c.647C>A | p.Ser216* | stop_gained, splice_region_variant | Exon 7 of 33 | ENST00000564138.6 | NP_002652.2 | |
PLCG2 | NM_001425749.1 | c.647C>A | p.Ser216* | stop_gained, splice_region_variant | Exon 8 of 34 | NP_001412678.1 | ||
PLCG2 | NM_001425750.1 | c.647C>A | p.Ser216* | stop_gained, splice_region_variant | Exon 7 of 33 | NP_001412679.1 | ||
PLCG2 | NM_001425751.1 | c.647C>A | p.Ser216* | stop_gained, splice_region_variant | Exon 8 of 34 | NP_001412680.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 7.24e-7 AC: 1AN: 1380598Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 690770 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
Age Distribution
GnomAD4 genome Cov.: 33
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at