rs753559567
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 5P and 6B. PM1PM5PP2BP4BP6BS2
The NM_017780.4(CHD7):c.6304G>T(p.Val2102Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2102G) has been classified as Uncertain significance.
Frequency
Consequence
NM_017780.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD7 | NM_017780.4 | c.6304G>T | p.Val2102Phe | missense_variant | 31/38 | ENST00000423902.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD7 | ENST00000423902.7 | c.6304G>T | p.Val2102Phe | missense_variant | 31/38 | 5 | NM_017780.4 | P1 | |
CHD7 | ENST00000524602.5 | c.1717-9200G>T | intron_variant | 1 | |||||
CHD7 | ENST00000695853.1 | c.6304G>T | p.Val2102Phe | missense_variant, NMD_transcript_variant | 31/37 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000458 AC: 67AN: 1461710Hom.: 0 Cov.: 32 AF XY: 0.0000495 AC XY: 36AN XY: 727138
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74322
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 04, 2016 | The V2102F variant in the CHD7 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. A missense variant in same residue (V2102I) has been reported in an individual diagnosed with CHARGE syndrome, however parental testing was not performed to determine if the variant was inherited or de novo (Félix et al., 2006). In addition, functional studies of the V2102I variant did not show a disruption defect between CHD7 and CHD8 (Batsukh et al., 2010). The V2102F variant was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The V2102F variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret V2102F as a variant of uncertain significance. - |
CHD7-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 17, 2023 | The CHD7 c.6304G>T variant is predicted to result in the amino acid substitution p.Val2102Phe. This variant has been previously observed in a cohort of individuals with CHARGE syndrome and reported as inherited (CHD7-28 in Table 2, Butcher et al. 2017. PubMed ID: 28475860). This variant is reported in 0.013% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-61765588-G-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
CHARGE syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 20, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at