rs864309543
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001271.4(CHD2):c.4233_4236delAGAA(p.Glu1412fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000659 in 151,730 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
CHD2
NM_001271.4 frameshift
NM_001271.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.74
Genes affected
CHD2 (HGNC:1917): (chromodomain helicase DNA binding protein 2) The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-93002269-CAAAG-C is Pathogenic according to our data. Variant chr15-93002269-CAAAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 218392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000660 AC: 1AN: 151614Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
1
AN:
151614
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.00000659 AC: 1AN: 151730Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74110
GnomAD4 genome
AF:
AC:
1
AN:
151730
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74110
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy 94 Pathogenic:2
| Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 18, 2024 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 04, 2020 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CHD2 are known to be pathogenic (PMID: 23708187, 24207121). This variant has been observed in an individual affected with genetic generalized epilepsy (PMID: 25783594). ClinVar contains an entry for this variant (Variation ID: 218392). This variant is present in population databases (rs768249023, ExAC 0.02%). This sequence change creates a premature translational stop signal (p.Glu1412Glyfs*64) in the CHD2 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at