Submissions for variant NM_013275.6(ANKRD11):c.7062dup (p.Ser2355fs)

dbSNP: rs886041942

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001386366	SCV001586558	pathogenic	KBG syndrome	2022-06-20	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1073378). This variant has not been reported in the literature in individuals affected with ANKRD11-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser2355Leufs*177) 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).
Provincial Medical Genetics Program of British Columbia, University of British Columbia	RCV001386366	SCV002320819	pathogenic	KBG syndrome	2022-01-01	criteria provided, single submitter	clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV001386366	SCV004009669	pathogenic	KBG syndrome	2022-09-23	criteria provided, single submitter	research
PreventionGenetics, part of Exact Sciences	RCV003416307	SCV004108017	pathogenic	ANKRD11-related disorder	2023-01-31	criteria provided, single submitter	clinical testing	The ANKRD11 c.7062dupC variant is predicted to result in a frameshift and premature protein termination (p.Ser2355Leufs*177). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in ANKRD11 are expected to be pathogenic, and therefore we interpret c.7062dup (p.Ser2355Leufs*177) as pathogenic.