Submissions for variant NM_006361.6(HOXB13):c.62C>G (p.Ala21Gly)

dbSNP: rs772484566

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001327027	SCV001518085	uncertain significance	not provided	2024-10-16	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 21 of the HOXB13 protein (p.Ala21Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HOXB13-related conditions. ClinVar contains an entry for this variant (Variation ID: 690937). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics	RCV002363195	SCV002660969	uncertain significance	Hereditary cancer-predisposing syndrome	2019-05-06	criteria provided, single submitter	clinical testing	The p.A21G variant (also known as c.62C>G), located in coding exon 1 of the HOXB13 gene, results from a C to G substitution at nucleotide position 62. The alanine at codon 21 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV001327027	SCV003837301	uncertain significance	not provided	2022-09-01	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Laboratory of Virology, Microbiology, Quality and Medical Biotechnologies, Faculty of Sciences and Techniques - Mohammedia, Hassan II University of Casablanca	RCV000856240	SCV000994231	uncertain significance	Prostate cancer, hereditary, 1		no assertion criteria provided	clinical testing