ClinVar Miner

Submissions for variant NM_012448.4(STAT5B):c.2161G>A (p.Gly721Ser)

gnomAD frequency: 0.00010  dbSNP: rs750095303
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000694293 SCV000822730 uncertain significance Growth hormone insensitivity with immune dysregulation 1, autosomal recessive 2023-12-22 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 721 of the STAT5B protein (p.Gly721Ser). This variant is present in population databases (rs750095303, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with STAT5B-related conditions. ClinVar contains an entry for this variant (Variation ID: 572813). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Blueprint Genetics RCV000788308 SCV000927367 uncertain significance not provided 2017-08-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003489815 SCV004241379 uncertain significance not specified 2023-12-20 criteria provided, single submitter clinical testing Variant summary: STAT5B c.2161G>A (p.Gly721Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 251268 control chromosomes. To our knowledge, no occurrence of c.2161G>A in individuals affected with Growth Hormone Insensitivity Syndrome With Immune Dysregulation 2, Autosomal Dominant and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Breakthrough Genomics, Breakthrough Genomics RCV000788308 SCV005192866 uncertain significance not provided criteria provided, single submitter not provided
Mayo Clinic Laboratories, Mayo Clinic RCV000788308 SCV005412713 uncertain significance not provided 2024-05-30 criteria provided, single submitter clinical testing BP4, PP2

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