ClinVar Miner

Submissions for variant NM_005249.5(FOXG1):c.251C>A (p.Pro84His)

gnomAD frequency: 0.00004  dbSNP: rs866815665
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel RCV003448305 SCV004175930 benign FOXG1 disorder 2023-10-13 reviewed by expert panel curation The p.Pro84His variant in FOXG1 is present in 1 individual in gnomAD (0.0039%) (not sufficient to meet BS1 criteria). The p.Pro84His variant is observed in at least 20 unaffected individuals (internal database - GeneDx; internal database - Invitae) (BS2). The p.Pro84His variant is found in at least 4 patients with an alternate molecular basis of disease (internal database - Invitae; internal database - GeneDx) (BP5_strong). Computational analysis prediction tools suggest that the p.Pro84His variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Pro84His variant in FOXG1 is classified as Benign based on the ACMG/AMP criteria (BS2, BP5_strong, BP4).
GeneDx RCV000585314 SCV000518070 likely benign not provided 2018-07-30 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000585314 SCV000692784 uncertain significance not provided 2017-10-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001365335 SCV001561601 benign Rett syndrome, congenital variant 2023-11-15 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004689733 SCV005185185 likely benign not specified 2024-05-21 criteria provided, single submitter clinical testing Variant summary: FOXG1 c.251C>A (p.Pro84His) 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 1.6e-05 in 1066578 control chromosomes. The observed variant frequency is approximately 15.94 fold of the estimated maximal expected allele frequency for a pathogenic variant in FOXG1 causing Rett Syndrome, Congenital Variant phenotype (1e-06). To our knowledge, no occurrence of c.251C>A in individuals affected with Rett Syndrome, Congenital Variant and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 380242). Based on the evidence outlined above, the variant was classified as likely benign.

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