Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000491014 | SCV000492514 | pathogenic | Epilepsy; Dysmorphic features; Intellectual disability | 2017-01-09 | criteria provided, single submitter | clinical testing | This nonsense variant has been observed in our laboratory homozygous in 4 probands: 20-year-old female with hemihypertrophy, intellectual disability, epilepsy, contractures, brachydactyly; 14-year-old male with IUGR, intellectual disability, SNHL, dystonia, epilepsy, dysmorphisms, short stature, microcephaly, contractures, scoliosis, hypogammaglobulinemia, brain abnormalities; 18-year-old female with hearing loss, epilepsy, dysmorphic features, microcephaly, failure to thrive, scoliosis, contractures, quadriplegia, hypothyroidism, intellectual disability, recurrent infections; 1-year-old female with developmental delays, hypotonia, dysmorphisms, microcephaly, congenital heart disease, unilateral retinoblastoma, reduced cerebral white matter, mild ventriculomegaly. One of these had a deceased sibling with similar features (not tested). An additional family was identified through research with 4 similarly affected sibs (2 deceased): 3 found to be homozygous, 1 not tested. Heterozygotes are expected to be asymptomatic carriers. |
| Gene |
RCV000578662 | SCV000680553 | pathogenic | not provided | 2022-01-21 | criteria provided, single submitter | clinical testing | Nonsense 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; This variant is associated with the following publications: (PMID: 28343629, 32924626) |
| Ambry Genetics | RCV001266980 | SCV001445161 | pathogenic | Inborn genetic diseases | 2022-08-17 | criteria provided, single submitter | clinical testing | The c.433C>T (p.R145*) alteration, located in exon 4 (coding exon 4) of the OTUD6B gene, consists of a C to T substitution at nucleotide position 433. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 145. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of 0.01% (36/240398) total alleles studied. The highest observed frequency was 0.09% (29/30828) of Latino alleles. This variant has been reported in the homozygous state in multiple unrelated individuals with syndromic intellectual disability (Santiago-Sim, 2017; Sánchez-Soler, 2020; Romero-Ibarguengoitia, 2020). Based on the available evidence, this alteration is classified as pathogenic. |
| Baylor Genetics | RCV000487564 | SCV001522456 | pathogenic | Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies | 2020-02-24 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Revvity Omics, |
RCV000487564 | SCV002020605 | pathogenic | Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies | 2021-05-05 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000578662 | SCV002235799 | pathogenic | not provided | 2023-04-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg145*) in the OTUD6B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OTUD6B are known to be pathogenic (PMID: 28343629). This variant is present in population databases (rs368313959, gnomAD 0.08%). This premature translational stop signal has been observed in individual(s) with an intellectual disability syndrome that includes seizures and facial dysmorphism (PMID: 28343629). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 375701). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000487564 | SCV000574728 | pathogenic | Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies | 2017-05-03 | no assertion criteria provided | literature only |