chr10-84194777-G-A
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Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PM2PP3PP5_Moderate
The NM_033100.4(CDHR1):c.17G>A(p.Trp6Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,372,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000022 ( 0 hom. )
Consequence
CDHR1
NM_033100.4 stop_gained
NM_033100.4 stop_gained
Scores
1
2
4
Clinical Significance
Conservation
PhyloP100: 0.578
Genes affected
CDHR1 (HGNC:14550): (cadherin related family member 1) This gene belongs to the cadherin superfamily of calcium-dependent cell adhesion molecules. The encoded protein is a photoreceptor-specific cadherin that plays a role in outer segment disc morphogenesis. Mutations in this gene are associated with inherited retinal dystrophies. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 71 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 10-84194777-G-A is Pathogenic according to our data. Variant chr10-84194777-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2796135.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDHR1 | NM_033100.4 | c.17G>A | p.Trp6Ter | stop_gained | 1/17 | ENST00000623527.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDHR1 | ENST00000623527.4 | c.17G>A | p.Trp6Ter | stop_gained | 1/17 | 1 | NM_033100.4 | P2 | |
CDHR1 | ENST00000332904.7 | c.17G>A | p.Trp6Ter | stop_gained | 1/17 | 1 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD4 exome AF: 0.00000219 AC: 3AN: 1372330Hom.: 0 Cov.: 31 AF XY: 0.00000443 AC XY: 3AN XY: 676886
GnomAD4 exome
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31
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3
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
Bravo
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 06, 2023 | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with inherited retinal dystrophy (PMID: 31387115). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp6*) in the CDHR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDHR1 are known to be pathogenic (PMID: 23044944, 23591405, 26103963, 26261414). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at