Submissions for variant NM_013275.6(ANKRD11):c.3224_3227del (p.Glu1075fs)

dbSNP: rs1064794330

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000487274	SCV000568864	pathogenic	not provided	2021-12-07	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 at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29258554, 28250421, 29453417, 25326635, 32476269)
Baylor Genetics	RCV000679909	SCV000807340	pathogenic	KBG syndrome	2017-09-01	criteria provided, single submitter	clinical testing	This frameshift mutation is categorized as deleterious according to ACMG guidelines (PMID:18414213). It was found once in our laboratory in an 8-year-old female with bipolar, PDD, ADHD, failure to thrive, leg length discrepancy, spondylolisthesis, dysmorphic features. Inherited from mother with psychiatric issues.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000679909	SCV001201503	pathogenic	KBG syndrome	2024-02-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu1075Glyfs*242) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with KBG syndrome (PMID: 28250421, 29453417). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 420179). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000679909	SCV001428770	pathogenic	KBG syndrome	2019-09-10	criteria provided, single submitter	clinical testing	This variant was identified as de novo (maternity and paternity confirmed).
CeGaT Center for Human Genetics Tuebingen	RCV000487274	SCV002498212	pathogenic	not provided	2022-03-01	criteria provided, single submitter	clinical testing	ANKRD11: PVS1, PM2
Genome Medicine, Institute for Basic Research in Developmental Disabilities	RCV000679909	SCV002562762	pathogenic	KBG syndrome		criteria provided, single submitter	clinical testing	KBG syndrome
Autoinflammatory diseases unit, CHU de Montpellier	RCV000679909	SCV001438092	pathogenic	KBG syndrome	2019-01-21	no assertion criteria provided	clinical testing