rs587776894
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001195263.2(PDZD7):โc.166_167insCโ(p.Arg56ProfsTer24) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000452 in 1,613,604 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (โ โ ). Synonymous variant affecting the same amino acid position (i.e. R56R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001195263.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDZD7 | NM_001195263.2 | c.166_167insC | p.Arg56ProfsTer24 | frameshift_variant | 2/17 | ENST00000619208.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDZD7 | ENST00000619208.6 | c.166_167insC | p.Arg56ProfsTer24 | frameshift_variant | 2/17 | 5 | NM_001195263.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152106Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461498Hom.: 0 Cov.: 35 AF XY: 0.0000468 AC XY: 34AN XY: 727066
GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152106Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74286
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | This sequence change creates a premature translational stop signal (p.Arg56Profs*24) in the PDZD7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PDZD7 are known to be pathogenic (PMID: 20440071). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with autosomal recessive non-syndromic hearing loss (PMID: 29048736). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30983). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 19, 2023 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26033081, 29048736, 31589614, 33105617, 20440071, 34416374) - |
Hearing loss, autosomal recessive 57 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2010 | - - |
Usher syndrome type 2A Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Jun 01, 2010 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at