Submissions for variant NM_013275.6(ANKRD11):c.4384dup (p.Arg1462fs)

dbSNP: rs886041521

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000331847	SCV000330191	pathogenic	not provided	2021-12-04	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: 30182498, 32581362)
Invitae	RCV001045250	SCV001209088	pathogenic	KBG syndrome	2023-07-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1462Lysfs*92) 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 clinical features of ANKRD11-related conditions (PMID: 30182498, 32581362). ClinVar contains an entry for this variant (Variation ID: 280288). For these reasons, this variant has been classified as Pathogenic.
Genetics Laboratory, UDIAT-Centre Diagnòstic, Hospital Universitari Parc Tauli	RCV001420203	SCV001622623	pathogenic	See cases	2021-04-26	criteria provided, single submitter	clinical testing	PVS1_very strong;PP5_strong;PM2_supporting
Provincial Medical Genetics Program of British Columbia, University of British Columbia	RCV001045250	SCV002320845	pathogenic	KBG syndrome	2022-01-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002519048	SCV003559761	pathogenic	Inborn genetic diseases	2021-07-23	criteria provided, single submitter	clinical testing	The c.4384dupA (p.R1462Kfs*92) alteration, located in exon 9 (coding exon 7) of the ANKRD11 gene, consists of a duplication of A at position 4384, causing a translational frameshift with a predicted alternate stop codon after 92 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from the Genome Aggregation Database (gnomAD), the ANKRD11 c.4384dupA alteration was not observed, with coverage at this position. This mutation was reported to be de novo in a patient with features consistent with KBG syndrome (Miao, 2018). Based on the available evidence, this alteration is classified as pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000331847	SCV004033513	pathogenic	not provided	2023-07-01	criteria provided, single submitter	clinical testing	ANKRD11: PVS1, PS2, PM2, PS4:Supporting
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003616	SCV001162027	pathogenic	Intellectual disability		no assertion criteria provided	research
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV001045250	SCV002569165	pathogenic	KBG syndrome		no assertion criteria provided	clinical testing