rs1329384177
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000367057.8(CR2):c.2863C>T(p.His955Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000367057.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CR2 | NM_001006658.3 | c.2863C>T | p.His955Tyr | missense_variant | 15/20 | ENST00000367057.8 | NP_001006659.1 | |
CR2 | NM_001877.5 | c.2686C>T | p.His896Tyr | missense_variant | 14/19 | NP_001868.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CR2 | ENST00000367057.8 | c.2863C>T | p.His955Tyr | missense_variant | 15/20 | 1 | NM_001006658.3 | ENSP00000356024 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152208Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461596Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727100
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Immunodeficiency, common variable, 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 12, 2017 | This sequence change replaces histidine with tyrosine at codon 955 of the CR2 protein (p.His955Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tyrosine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CR2-related disease. This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at