chr8-60801591-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_017780.4(CHD7):c.2440C>T(p.Gln814*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_017780.4 stop_gained, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.06e-7 AC: 1AN: 1415986Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 700448
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
CHARGE syndrome Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 16, 2018 | This sequence change creates a premature translational stop signal (p.Gln814*) in the CHD7 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900). This variant has been observed in individuals affected with CHD7-related disease (PMID: 23885230, 29300383) and has been reported to be de novo in an individual referred for CHARGE syndrome genetic testing (PMID: 21158681). ClinVar contains an entry for this variant (Variation ID: 488369). This variant is not present in population databases (ExAC no frequency). - |
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Pathogenic, no assertion criteria provided | research | Sbielas Lab-Department of Human Genetics University of Michigan, University of Michigan Medical School | Oct 27, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at