Submissions for variant NM_013275.6(ANKRD11):c.2408_2412del (p.Lys803fs)

dbSNP: rs886039902

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV000256444	SCV000323203	pathogenic	KBG syndrome	2016-09-15	criteria provided, single submitter	research
GeneDx	RCV000522964	SCV000618448	pathogenic	not provided	2021-03-18	criteria provided, single submitter	clinical testing	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 in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27667800, 25533962, 28191890, 29224748, 28135719, 32124548)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000256444	SCV000823257	pathogenic	KBG syndrome	2022-07-23	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individuals with KBG syndrome (PMID: 27667800). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 266033). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys803Argfs*5) in the ANKRD11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANKRD11 are known to be pathogenic (PMID: 21782149, 25125236, 25413698, 25652421).
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000256444	SCV000966193	pathogenic	KBG syndrome	2018-05-09	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000256444	SCV001429227	pathogenic	KBG syndrome	2020-03-09	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000522964	SCV001446488	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Institute for Human Genetics, University Hospital Essen	RCV001376675	SCV001478034	pathogenic	Global developmental delay	2021-01-22	criteria provided, single submitter	research
Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano	RCV000256444	SCV002097344	pathogenic	KBG syndrome	2021-11-01	criteria provided, single submitter	research
Fulgent Genetics, Fulgent Genetics	RCV000256444	SCV002784845	pathogenic	KBG syndrome	2021-07-06	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000522964	SCV002822334	pathogenic	not provided	2022-11-01	criteria provided, single submitter	clinical testing	ANKRD11: PVS1, PM2
Ambry Genetics	RCV002519008	SCV003636019	pathogenic	Inborn genetic diseases	2022-09-28	criteria provided, single submitter	clinical testing	The c.2408_2412delAAAAA (p.K803Rfs*5) alteration, located in exon 9 (coding exon 7) of the ANKRD11 gene, consists of a deletion of 5 nucleotides from position 2408 to 2412, causing a translational frameshift with a predicted alternate stop codon after 5 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported as de novo in multiple unrelated individuals with clinical features of KBG syndrome (Parenti, 2021; Gnazzo, 2020). Additional heterozygous individuals with ANKRD11 variants have been reported in the literature (Low, 2016; Bestetti, 2022). Based on the available evidence, this alteration is classified as pathogenic.
Laboratoire de Génétique Moléculaire, CHU Bordeaux	RCV000256444	SCV003836673	pathogenic	KBG syndrome	2020-05-28	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000522964	SCV004026190	pathogenic	not provided	2022-12-12	criteria provided, single submitter	clinical testing	PVS1
Autoinflammatory diseases unit, CHU de Montpellier	RCV000256444	SCV001438088	pathogenic	KBG syndrome	2016-04-15	no assertion criteria provided	clinical testing
GenomeConnect - Simons Searchlight	RCV000256444	SCV001443557	pathogenic	KBG syndrome	2018-09-10	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-09-10 and interpreted as Pathogenic. Variant was initially reported on 2018-01-09 by GTR ID of laboratory name 506154. The reporting laboratory might also submit to ClinVar.
PreventionGenetics, part of Exact Sciences	RCV004739645	SCV005343623	pathogenic	ANKRD11-related disorder	2024-03-25	no assertion criteria provided	clinical testing	The ANKRD11 c.2408_2412del5 variant is predicted to result in a frameshift and premature protein termination (p.Lys803Argfs*5). This variant has been reported in multiple unrelated individuals with KBG syndrome (Low et al. 2016. PubMed ID: 27667800; Bianchi et al. 2017. PubMed ID: 29224748; Wright et al. 2021. PubMed ID: 33149276; Parenti et al. 2021. PubMed ID: 33955014; Marangoni et al. 2021. PubMed ID: 34906519; Digilio et al. 2021. PubMed ID: 34971082; Tal-Ben Ishay et al. 2021. PubMed ID: 35052376; Loberti et al. 2022. PubMed ID: 35861666). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in ANKRD11 are expected to be pathogenic. This variant is interpreted as pathogenic.