chr3-184357485-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_004366.6(CLCN2):c.775G>A(p.Val259Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000118 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V259V) has been classified as Likely benign.
Frequency
Consequence
NM_004366.6 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCN2 | NM_004366.6 | c.775G>A | p.Val259Ile | missense_variant, splice_region_variant | 8/24 | ENST00000265593.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN2 | ENST00000265593.9 | c.775G>A | p.Val259Ile | missense_variant, splice_region_variant | 8/24 | 1 | NM_004366.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251268Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135834
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461826Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9AN XY: 727212
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
Seizure;C0338656:Cognitive impairment;C0856975:Autistic behavior;C1263846:Attention deficit hyperactivity disorder;C1835807:Prominent fingertip pads;C1849089:Broad forehead;C1850049:Clinodactyly of the 5th finger;C4551570:2-3 toe syndactyly;C5399973:Periventricular heterotopia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Personalized Medicine, Children's Hospital Los Angeles | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at