ClinVar Miner

Submissions for variant NM_001271938.2(MEGF8):c.6310G>T (p.Ala2104Ser)

gnomAD frequency: 0.00001  dbSNP: rs772768716
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000680166 SCV000807640 uncertain significance MEGF8-related Carpenter syndrome 2017-09-01 criteria provided, single submitter clinical testing Likely pathogenicity based on finding it once in our laboratory in trans with another missense variant in a 1-year-old male with metopic craniosynostosis, global delays, dysmorphisms, short neck, inverted npples, structural brain anomalies, ptosis, strabismus, rocker bottom feet, adducted thumbs, contractures, cafe au lait macules. Heterozygotes would be expected to be asymptomatic carriers.
Invitae RCV000680166 SCV000812391 uncertain significance MEGF8-related Carpenter syndrome 2022-06-28 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2037 of the MEGF8 protein (p.Ala2037Ser). This variant is present in population databases (rs772768716, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with MEGF8-related conditions. ClinVar contains an entry for this variant (Variation ID: 561156). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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.
GeneDx RCV001756146 SCV001986747 uncertain significance not provided 2021-04-29 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: 25326635, 28492532)

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