1-109250554-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001408.3(CELSR2):c.475G>A(p.Gly159Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,613,900 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
NM_001408.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CELSR2 | NM_001408.3 | c.475G>A | p.Gly159Arg | missense_variant | 1/34 | ENST00000271332.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CELSR2 | ENST00000271332.4 | c.475G>A | p.Gly159Arg | missense_variant | 1/34 | 1 | NM_001408.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000718 AC: 18AN: 250586Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135632
GnomAD4 exome AF: 0.000116 AC: 169AN: 1461672Hom.: 0 Cov.: 71 AF XY: 0.000121 AC XY: 88AN XY: 727100
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74372
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 27, 2022 | The c.475G>A (p.G159R) alteration is located in exon 1 (coding exon 1) of the CELSR2 gene. This alteration results from a G to A substitution at nucleotide position 475, causing the glycine (G) at amino acid position 159 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 159 of the CELSR2 protein (p.Gly159Arg). This variant is present in population databases (rs758600773, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CELSR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1361646). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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