rs1554607313
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_017780.4(CHD7):c.8744delG(p.Gly2915AspfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,366 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
CHD7
NM_017780.4 frameshift
NM_017780.4 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.55
Publications
0 publications found
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]
CHD7 Gene-Disease associations (from GenCC):
- CHARGE syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Broad Center for Mendelian Genomics, ClinGen, G2P
- hypogonadotropic hypogonadism 5 with or without anosmiaInheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- hypogonadotropic hypogonadismInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Kallmann syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Omenn syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1454366Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 722424 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1454366
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
722424
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33162
American (AMR)
AF:
AC:
0
AN:
44240
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25746
East Asian (EAS)
AF:
AC:
0
AN:
39576
South Asian (SAS)
AF:
AC:
0
AN:
85824
European-Finnish (FIN)
AF:
AC:
0
AN:
53196
Middle Eastern (MID)
AF:
AC:
0
AN:
5732
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1106910
Other (OTH)
AF:
AC:
0
AN:
59980
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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