Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000319353 | SCV000329590 | pathogenic | not provided | 2020-03-16 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23643382, 25394172, 20536592, 25497574, 29419413, 32724172) |
Reproductive Endocrine Unit, |
RCV001542473 | SCV003932548 | pathogenic | Hypogonadotropic hypogonadism 2 with or without anosmia | 2023-05-04 | criteria provided, single submitter | research | The variant has been classified as P2 based on the variant meeting the following ACMG Criteria: PS2,PM2,PP3,PP1,PP2. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004537181 | SCV004122482 | pathogenic | FGFR1-related disorder | 2023-10-31 | criteria provided, single submitter | clinical testing | Variant summary: FGFR1 c.1042G>A (p.Gly348Arg) results in a non-conservative amino acid change located in the Immunoglobulin subtype 2 (IPR003598) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249898 control chromosomes. c.1042G>A has been reported in the literature in individuals affected with autosomal dominant congenital hypogonadotropic hypogonadism and Kallmann syndrome, including at-least two de novo occurences (example, Acierno_2020, Zhang_2021, BailleulForestier_2010). These data indicate that the variant is very likely associated with FGFR1-Related Disorders. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in diminished response of fibroblast growth factor 8 stimulation (Acierno_2020). The following publications have been ascertained in the context of this evaluation (PMID: 32724172, 34348883, 20536592). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
OMIM | RCV000043588 | SCV000071606 | risk factor | Hypogonadotropic hypogonadism 2 with anosmia | 2015-08-01 | no assertion criteria provided | literature only | |
Genomics England Pilot Project, |
RCV001542473 | SCV001760212 | pathogenic | Hypogonadotropic hypogonadism 2 with or without anosmia | no assertion criteria provided | clinical testing | ||
Prevention |
RCV004537181 | SCV005366101 | pathogenic | FGFR1-related disorder | 2024-08-30 | no assertion criteria provided | clinical testing | The FGFR1 c.1042G>A variant is predicted to result in the amino acid substitution p.Gly348Arg. This variant has been reported in many individuals with Kallmann syndrome and hypogonadotropic hypogonadism (Bailleul-Forestier et al. 2010. PubMed ID: 20536592; Table S3, Miraoui et al. 2013. PubMed ID: 23643382; Table S2, Cassatella et al. 2018. PubMed ID: 29419413; Acierno et al. 2020. PubMed ID: 32724172). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic. |