Submissions for variant NM_005751.5(AKAP9):c.8286A>C (p.Lys2762Asn)

gnomAD frequency: 0.00093  dbSNP: rs144875383

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171724	SCV000055233	likely benign	not provided	2013-06-24	criteria provided, single submitter	research
Eurofins Ntd Llc (ga)	RCV000171724	SCV000229669	uncertain significance	not provided	2015-01-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000241571	SCV000319822	likely benign	Cardiovascular phenotype	2019-01-10	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084749	SCV000563335	likely benign	Long QT syndrome	2025-01-28	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000624954	SCV000743176	likely benign	Long QT syndrome 11	2014-10-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001192966	SCV001361459	benign	not specified	2019-11-26	criteria provided, single submitter	clinical testing	Variant summary: AKAP9 c.8286A>C (p.Lys2762Asn) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.001 in 250844 control chromosomes, predominantly at a frequency of 0.0019 within the Non-Finnish European subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 190 fold higher than the estimated maximal expected allele frequency for a pathogenic variant in AKAP9 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is a benign polymorphism. c.8286A>C has been reported in the literature in heterozygous individuals without ECG signs of Long QT Syndrome (Ghouse_2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submissions (evaluation after 2014) cite the variant twice as likely benign and once as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000171724	SCV004164294	benign	not provided	2022-05-01	criteria provided, single submitter	clinical testing	AKAP9: BS1, BS2
Clinical Genetics, Academic Medical Center	RCV001192966	SCV001917737	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000171724	SCV001958389	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003907542	SCV004728332	likely benign	AKAP9-related disorder	2022-06-13	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).