rs143614333
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001006658.3(CR2):c.1676G>A(p.Gly559Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000625 in 1,613,946 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001006658.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000631 AC: 96AN: 152078Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000848 AC: 213AN: 251304Hom.: 1 AF XY: 0.000781 AC XY: 106AN XY: 135808
GnomAD4 exome AF: 0.000625 AC: 913AN: 1461750Hom.: 4 Cov.: 32 AF XY: 0.000653 AC XY: 475AN XY: 727174
GnomAD4 genome AF: 0.000631 AC: 96AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44AN XY: 74396
ClinVar
Submissions by phenotype
Immunodeficiency, common variable, 7 Uncertain:2Benign:1
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This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
not provided Uncertain:2Benign:1
The G559E variant in the CR2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G559E variant is observed in 79/66693 (0.118%) alleles from individuals of non-Finnish European background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G559E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G559E as a variant of uncertain significance. -
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CR2: BS2 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at