ClinVar Miner

Submissions for variant NM_013275.6(ANKRD11):c.7607G>A (p.Arg2536Gln)

dbSNP: rs2033511172
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001310342 SCV001500097 uncertain significance not provided 2020-09-01 criteria provided, single submitter clinical testing
GeneDx RCV001310342 SCV002097460 pathogenic not provided 2024-08-05 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 37226940, 37964495, 35970914, 34440431)
Genome Medicine, Institute for Basic Research in Developmental Disabilities RCV002275348 SCV002562769 likely pathogenic KBG syndrome criteria provided, single submitter clinical testing KBG syndrome
Dr. med. U. Finckh, Human Genetics, Eurofins MVZ RCV002275348 SCV004037197 likely pathogenic KBG syndrome 2022-12-05 criteria provided, single submitter clinical testing Heterozygous in a proband with suspected KBG syndrome (based on clinical examination and algorithms for facial image analysis). Subsequently, also detected in the apparently unaffected mother, thus not supporting a pathogenic relevance of this variant, in first place (internal data). However, the variant has since been classified as likely pathogenic in another publication (PMID: 35970914) and is now rated once each as pathogenic, likely pathogenic, and VUS in ClinVar. It has been detected in at least three patients with phenotype consistent with KBG syndrome (partially confirmed de novo) and is not found in >125.000 individuals of the general population (gnomAD v2). Apparently, maternal inheritance was also reported once (PMID: 35970914). Overall, the inheritance of causal ANKRD11 variants without signs of KBG syndrome in the corresponding parent seems possible (somatic mosaic, variable expressivity, intrafamilial variability, female patients seem to be less severely affected; Gene Reviews: NBK487886, PMID: 29258554). Thus, we classify the variant as likely pathogenic. Further information however may lead to up- or downrating and therefore should be followed closely.

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