chr8-60823837-T-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_017780.4(CHD7):c.3202-3T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
CHD7
NM_017780.4 splice_region, splice_polypyrimidine_tract, intron
NM_017780.4 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.9989
1
Clinical Significance
Conservation
PhyloP100: 0.355
Genes affected
CHD7 (HGNC:20626): (chromodomain helicase DNA binding protein 7) This gene encodes a protein that contains several helicase family domains. Mutations in this gene have been found in some patients with the CHARGE syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 8-60823837-T-G is Pathogenic according to our data. Variant chr8-60823837-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 411184.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD7 | NM_017780.4 | c.3202-3T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000423902.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD7 | ENST00000423902.7 | c.3202-3T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_017780.4 | P1 | |||
CHD7 | ENST00000524602.5 | c.1717-38392T>G | intron_variant | 1 | |||||
CHD7 | ENST00000525508.1 | c.3202-3T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
CHD7 | ENST00000695853.1 | c.3202-3T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CHARGE syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 30, 2016 | In summary, this is a rare intronic variant which has been observed de novo in affected individuals. For these reasons it has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. This variant has been shown to arise de novo in individuals affected with CHARGE syndrome (PMID: 22033296). Family studies have indicated that this variant was not present in the parents of this individual, which suggests that it was de novo in that affected individual (Invitae database). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 12 of the CHD7 gene. It does not directly change the encoded amino acid sequence of the CHD7 protein. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 1
DS_AL_spliceai
Position offset: 3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at