Submissions for variant NM_003640.5(ELP1):c.2855A>T (p.Lys952Ile)

gnomAD frequency: 0.01592  dbSNP: rs2230798

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000249304	SCV000309751	benign	not specified		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000857357	SCV000563267	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000465354	SCV000743224	benign	Familial dysautonomia	2014-10-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000465354	SCV001329066	likely benign	Familial dysautonomia	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000249304	SCV001363974	benign	not specified	2019-02-22	criteria provided, single submitter	clinical testing	Variant summary: IKBKAP c.2855A>T (p.Lys952Ile) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.016 in 276918 control chromosomes in the gnomAD database, including 53 homozygotes. The observed variant frequency is approximately 8.5 fold of the estimated maximal expected allele frequency for a pathogenic variant in IKBKAP causing Familial Dysautonomia phenotype (0.0018), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.2855A>T in individuals affected with Familial Dysautonomia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000857357	SCV001474251	benign	not provided	2023-11-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000857357	SCV001848159	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000857357	SCV005224841	likely benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000249304	SCV001923892	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000465354	SCV002082061	likely benign	Familial dysautonomia	2018-03-30	no assertion criteria provided	clinical testing