ClinVar Miner

Submissions for variant NM_012448.4(STAT5B):c.2353G>A (p.Ala785Thr)

gnomAD frequency: 0.00003  dbSNP: rs760771231
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001281001 SCV001468397 uncertain significance Growth hormone insensitivity with immune dysregulation 1, autosomal recessive; Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant 2021-03-30 criteria provided, single submitter clinical testing STAT5B NM_012448.3 exon 19 p.Ala785Thr (c.2353G>A): This variant has not been reported in the literature but is present in 0.01% (4/30612) of South Asian alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/17-40353767-C-T?dataset=gnomad_r2_1). This variant amino acid Threonine (Thr) is present in 5 species (naked mole rat, guinea pig, chinchilla, coelacanth, lamprey); this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001325583 SCV001516579 uncertain significance Growth hormone insensitivity with immune dysregulation 1, autosomal recessive 2023-11-25 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 785 of the STAT5B protein (p.Ala785Thr). This variant is present in population databases (rs760771231, 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: 992531). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The threonine 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.

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