Submissions for variant NM_003721.4(RFXANK):c.445G>A (p.Asp149Asn)

gnomAD frequency: 0.00216  dbSNP: rs115220304

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000647953	SCV000769762	likely benign	MHC class II deficiency	2024-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000647953	SCV001283929	likely benign	MHC class II deficiency	2018-01-12	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000647953	SCV001468360	uncertain significance	MHC class II deficiency	2021-03-30	criteria provided, single submitter	clinical testing	RFXANK NM_003721.3 exon 7 p.Asp149Asn (c.445G>A): This variant has not been reported in the literature but is present in 0.6% (169/24938) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/19-19308922-G-A?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:538596). This variant Asparagine is present as wild type in 1 animal (Opossum); however, evolutionary conservation suggests that this variant may impact the protein. Computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
PreventionGenetics, part of Exact Sciences	RCV003945639	SCV004758815	likely benign	RFXANK-related condition	2020-08-19	criteria provided, single submitter	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).