chr2-232529965-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BS1_SupportingBS2
The NM_000751.3(CHRND):c.646C>T(p.Arg216Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,614,110 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000751.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHRND | NM_000751.3 | c.646C>T | p.Arg216Trp | missense_variant | Exon 7 of 12 | ENST00000258385.8 | NP_000742.1 | |
CHRND | NM_001256657.2 | c.601C>T | p.Arg201Trp | missense_variant | Exon 6 of 11 | NP_001243586.1 | ||
CHRND | NM_001311196.2 | c.343C>T | p.Arg115Trp | missense_variant | Exon 7 of 12 | NP_001298125.1 | ||
CHRND | NM_001311195.2 | c.238+1309C>T | intron_variant | Intron 5 of 9 | NP_001298124.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000217 AC: 54AN: 249248Hom.: 0 AF XY: 0.000282 AC XY: 38AN XY: 134912
GnomAD4 exome AF: 0.000143 AC: 209AN: 1461808Hom.: 3 Cov.: 32 AF XY: 0.000183 AC XY: 133AN XY: 727206
GnomAD4 genome AF: 0.0000985 AC: 15AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74482
ClinVar
Submissions by phenotype
Lethal multiple pterygium syndrome Uncertain:1
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 216 of the CHRND protein (p.Arg216Trp). This variant is present in population databases (rs777271963, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with CHRND-related conditions. ClinVar contains an entry for this variant (Variation ID: 570038). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CHRND protein function. 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. -
not provided Uncertain:1
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CHRND-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at