rs201017642
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001006658.3(CR2):c.424C>T(p.Arg142Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000755 in 1,601,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001006658.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CR2 | NM_001006658.3 | c.424C>T | p.Arg142Ter | stop_gained | 2/20 | ENST00000367057.8 | |
CR2 | NM_001877.5 | c.424C>T | p.Arg142Ter | stop_gained | 2/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CR2 | ENST00000367057.8 | c.424C>T | p.Arg142Ter | stop_gained | 2/20 | 1 | NM_001006658.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000669 AC: 16AN: 239128Hom.: 0 AF XY: 0.0000852 AC XY: 11AN XY: 129132
GnomAD4 exome AF: 0.0000814 AC: 118AN: 1449520Hom.: 0 Cov.: 32 AF XY: 0.0000916 AC XY: 66AN XY: 720320
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74282
ClinVar
Submissions by phenotype
Immunodeficiency, common variable, 7 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | This sequence change creates a premature translational stop signal (p.Arg142*) in the CR2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CR2 are known to be pathogenic (PMID: 26325596, 28499783). This variant is present in population databases (rs201017642, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with hypogammaglobulinemia (PMID: 26325596). ClinVar contains an entry for this variant (Variation ID: 540314). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at