Submissions for variant NM_199242.3(UNC13D):c.972C>T (p.Asp324=)

gnomAD frequency: 0.00029  dbSNP: rs368990813

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000768127	SCV000406677	uncertain significance	Familial hemophagocytic lymphohistiocytosis 3	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768127	SCV000899071	uncertain significance	Familial hemophagocytic lymphohistiocytosis 3	2021-03-30	criteria provided, single submitter	clinical testing	UNC13D NM_199242 exon 12 p.Asp324Asp (c.972C>T):This variant has not been reported in the literature but is present in 28/126298 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs368990813). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is present in ClinVar (Variation ID:325268). Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae	RCV000768127	SCV001031068	likely benign	Familial hemophagocytic lymphohistiocytosis 3	2024-01-18	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001820977	SCV002065434	likely benign	not specified	2021-12-16	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263030	SCV002543202	uncertain significance	Autoinflammatory syndrome	2020-05-01	criteria provided, single submitter	clinical testing