ClinVar Miner

Submissions for variant NM_203447.4(DOCK8):c.3079G>A (p.Val1027Ile)

gnomAD frequency: 0.00001  dbSNP: rs199782622
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003595835 SCV001732986 benign Autosomal recessive hyper-IgE syndrome 2023-11-21 criteria provided, single submitter clinical testing
GeneDx RCV001555076 SCV001776430 likely benign not provided 2020-12-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28750028)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271658 SCV002555909 benign not specified 2022-06-15 criteria provided, single submitter clinical testing Variant summary: DOCK8 c.3079G>A (p.Val1027Ile) results in a 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 0.00041 in 251394 control chromosomes (gnomAD), predominantly at a frequency of 0.0032 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 9 fold of the estimated maximal expected allele frequency for a pathogenic variant in DOCK8 causing Severe Combined Immunodeficiency (0.00035), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.3079G>A has been reported in the literature in one individual with Hyper IgE Syndrome (Omoyinmi_2017). This report does not provide unequivocal conclusions about association of the variant with Severe Combined Immunodeficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: one classified the variant as likely benign and the other as benign. Based on the evidence outlined above, the variant was classified as benign.

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