11-14878277-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_024514.5(CYP2R1):c.1351G>A(p.Glu451Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,612,884 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 Uncertain significance (★).
Frequency
Consequence
NM_024514.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP2R1 | ENST00000334636.10 | c.1351G>A | p.Glu451Lys | missense_variant | Exon 5 of 5 | 1 | NM_024514.5 | ENSP00000334592.5 | ||
CYP2R1 | ENST00000532805.1 | n.*459G>A | non_coding_transcript_exon_variant | Exon 4 of 4 | 5 | ENSP00000465097.1 | ||||
CYP2R1 | ENST00000532805.1 | n.*459G>A | 3_prime_UTR_variant | Exon 4 of 4 | 5 | ENSP00000465097.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152118Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000320 AC: 8AN: 250258Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135340
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1460766Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 726670
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74316
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 451 of the CYP2R1 protein (p.Glu451Lys). This variant is present in population databases (rs782741911, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CYP2R1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at