ClinVar Miner

Submissions for variant NM_012330.4(KAT6B):c.4203_4204CT[1] (p.Ser1402fs) (rs199470477)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000623297 SCV000741447 pathogenic Inborn genetic diseases 2016-04-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
GeneDx RCV000128652 SCV000322054 pathogenic not provided 2018-03-22 criteria provided, single submitter clinical testing The c.4205_4206delCT pathogenic variant in the KAT6B gene has been reported previously in at least two individuals with a clinical diagnosis of Ohdo syndrome (Clayton-Smith et al., 2011). This variant causes a frameshift starting with codon Serine 1402, changes this amino acid to a Cysteine residue, and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Ser1402CysfsX5. This variant is predicted to cause loss of normal protein function through protein truncation, as the last 672 amino acids of the protein are replaced with 4 incorrect amino acids. The c.4205_4206delCT variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.4205_4206delCT as a pathogenic variant.
GeneReviews RCV000032258 SCV000055892 pathologic Young Simpson syndrome 2012-12-13 no assertion criteria provided curation Converted during submission to Pathogenic.
Invitae RCV000641704 SCV000763352 pathogenic Genitopatellar syndrome 2018-09-28 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the KAT6B gene (p.Ser1402Cysfs*5). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 672 amino acids of the KAT6B protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in individuals affected with KAT6B-related conditions (PMID: 22077973, 28696035) and has been reported in individuals affected with genitopatellar syndrome or Say-Barber-Biesecker-Young-Simpson syndrome (PMID: 22077973, 25424711, Invitae). ClinVar contains an entry for this variant (Variation ID: 39001). For these reasons, this variant has been classified as Pathogenic.
Lee Lab(KAT6B), Baylor College of Medicine RCV000128652 SCV000172292 not provided not provided no assertion provided not provided

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