chr8-60795071-G-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_017780.4(CHD7):āc.2182G>Cā(p.Asp728His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000929 in 1,613,782 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. D728E) has been classified as Likely benign.
Frequency
Consequence
NM_017780.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD7 | NM_017780.4 | c.2182G>C | p.Asp728His | missense_variant | 4/38 | ENST00000423902.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD7 | ENST00000423902.7 | c.2182G>C | p.Asp728His | missense_variant | 4/38 | 5 | NM_017780.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000642 AC: 16AN: 249174Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135176
GnomAD4 exome AF: 0.0000937 AC: 137AN: 1461604Hom.: 0 Cov.: 31 AF XY: 0.0000963 AC XY: 70AN XY: 727080
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74350
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 31, 2016 | The p.D728H variant (also known as c.2182G>C), located in coding exon 3 of the CHD7 gene, results from a G to C substitution at nucleotide position 2182. The aspartic acid at codon 728 is replaced by histidine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 5907 samples (11814 alleles) with coverage at this position. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Amenorrhea Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Yale Center for Mendelian Genomics, Yale University | Mar 08, 2021 | - - |
CHARGE syndrome;C3552553:Hypogonadotropic hypogonadism 5 with or without anosmia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 03, 2022 | - - |
CHARGE syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at