1-207454457-C-CG
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001006658.3(CR2):c.40dupG(p.Val14GlyfsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,427,414 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. V14V) has been classified as Likely benign.
Frequency
Consequence
NM_001006658.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 7.01e-7 AC: 1AN: 1427414Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 708812
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Immunodeficiency, common variable, 7 Pathogenic:1
This sequence change creates a premature translational stop signal (p.Val14Glyfs*22) 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). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with CR2-related conditions. This variant is present in population databases (rs750238787, gnomAD 0.001%). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at