rs1015228436
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBS2
The NM_001271.4(CHD2):c.3237+5T>G variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,453,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001271.4 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD2 | NM_001271.4 | c.3237+5T>G | splice_donor_5th_base_variant, intron_variant | ENST00000394196.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD2 | ENST00000394196.9 | c.3237+5T>G | splice_donor_5th_base_variant, intron_variant | 5 | NM_001271.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000412 AC: 1AN: 242640Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 131326
GnomAD4 exome AF: 0.00000344 AC: 5AN: 1453198Hom.: 0 Cov.: 30 AF XY: 0.00000415 AC XY: 3AN XY: 722734
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy 94 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 15, 2023 | This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change falls in intron 25 of the CHD2 gene. It does not directly change the encoded amino acid sequence of the CHD2 protein. It affects a nucleotide within the consensus splice site. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 474382). This variant has not been reported in the literature in individuals affected with CHD2-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at