Submissions for variant NM_000061.3(BTK):c.141+11C>T

gnomAD frequency: 0.00620  dbSNP: rs138411530

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224614	SCV000281500	benign	not provided	2015-10-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000380244	SCV000481396	likely benign	X-linked agammaglobulinemia with growth hormone deficiency	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000266994	SCV000481397	likely benign	X-linked agammaglobulinemia	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.
GeneDx	RCV000445094	SCV000512427	benign	not specified	2015-08-17	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000224614	SCV000695289	benign	not provided	2017-03-03	criteria provided, single submitter	clinical testing	Variant summary: The BTK c.141+11C>T variant involves the alteration of a non-conserved intronic nucleotide. Mutation tested predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. These predictions have yet to be confirmed by functional studies. This variant was found in the large control population database ExAC (410/87888 control chromosomes including 160 hemizygotes) at a frequency of 0.004665, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic BTK variant (0.0023049), suggesting this variant is likely a benign polymorphism. Multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign or benign. Published studies als support for benign outcome -- this variant was found not to cosegregate with XLA in a family (Conley_2008) and was found in a family with primary immunodeficiency disease that had alternate molecular mechanism (Stray-Pedersen_2017). Taken together, this variant is classified as benign.
Eurofins Ntd Llc (ga)	RCV000445094	SCV000704471	benign	not specified	2016-12-28	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000660378	SCV000782453	uncertain significance	X-linked agammaglobulinemia; X-linked agammaglobulinemia with growth hormone deficiency	2016-06-23	criteria provided, single submitter	clinical testing
Mendelics	RCV000266994	SCV001141973	likely benign	X-linked agammaglobulinemia	2019-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000380244	SCV001722820	benign	X-linked agammaglobulinemia with growth hormone deficiency	2025-02-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000224614	SCV004167261	benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	BTK: BP4, BS1, BS2