Submissions for variant NM_000101.4(CYBA):c.524CGG[3] (p.Ala176dup)

dbSNP: rs760275837

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000726743	SCV000564920	likely benign	not provided	2019-09-09	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000726743	SCV000702667	uncertain significance	not provided	2016-11-17	criteria provided, single submitter	clinical testing
Invitae	RCV000642285	SCV000763954	uncertain significance	Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	2024-01-29	criteria provided, single submitter	clinical testing	This variant, c.527_529dup, results in the insertion of 1 amino acid(s) of the CYBA protein (p.Ala176dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs760275837, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with CYBA-related conditions. ClinVar contains an entry for this variant (Variation ID: 418151). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000642285	SCV000898644	uncertain significance	Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	2021-03-30	criteria provided, single submitter	clinical testing	CYBA NM_000101.3 exon 6 p.Ala176dup (c.527_529dup): This variant has not been reported in the literature but is present in 33/51894 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs760275837). This variant is present in ClinVar (Variation ID:418151). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant represents a duplication of 1 amino acid at position 176 and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Center for Human Genetics Tuebingen	RCV000726743	SCV002063536	uncertain significance	not provided	2021-11-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003987555	SCV004803658	likely benign	not specified	2024-01-23	criteria provided, single submitter	clinical testing	Variant summary: CYBA c.527_529dupCGG (p.Ala176dup) results in an in-frame duplication that is predicted to duplicate one amino acids into the encoded protein. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.29 fold of the estimated maximal expected allele frequency for a pathogenic variant in CYBA causing Chronic Granulomatous Disease phenotype (0.00061), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.527_529dupCGG in individuals affected with Chronic Granulomatous Disease and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 418151). Based on the evidence outlined above, the variant was classified as likely benign.
Natera, Inc.	RCV001271479	SCV001452668	uncertain significance	Chronic granulomatous disease	2020-01-17	no assertion criteria provided	clinical testing