ClinVar Miner

Submissions for variant NM_016592.5(GNAS):c.*42+12917C>T

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354116 SCV001548652 uncertain significance Pseudohypoparathyroidism type 1B no assertion criteria provided clinical testing The GNAS p.Q180* variant was identified in the literature in a cohort of 379,768 UK Biobank participants of European ancestry at a minor allele frequency of 0.03063 and was classified as a benign variant for albright hereditary osteodystrophy (Wright_2019_PMID_30665703). The variant was identified in dbSNP (ID: rs200910410) but was not identified in ClinVar. The variant was identified in control databases in 28 of 267434 chromosomes at a frequency of 0.0001047, where it was observed only in the European (non-Finnish) population in 28 of 121272 chromosomes (freq: 0.0002309) (Genome Aggregation Database March 6, 2019, v2.1.1). The c.538C>T variant leads to a premature stop codon at position 180 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the GNAS gene are an established mechanism of disease in progressive osseous heteroplasia, Pseudohypoparathyroidism Ib, Pseudohypoparathyroidism Ia and is the type of variant expected to cause the disorder. However, the frequency of this loss of function variant is greater than expected for these conditions. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354967 SCV001549705 uncertain significance Progressive osseous heteroplasia no assertion criteria provided clinical testing The GNAS p.Q180* variant was identified in the literature in a cohort of 379,768 UK Biobank participants of European ancestry at a minor allele frequency of 0.03063 and was classified as a benign variant for albright hereditary osteodystrophy (Wright_2019_PMID_30665703). The variant was identified in dbSNP (ID: rs200910410) but was not identified in ClinVar. The variant was identified in control databases in 28 of 267434 chromosomes at a frequency of 0.0001047, where it was observed only in the European (non-Finnish) population in 28 of 121272 chromosomes (freq: 0.0002309) (Genome Aggregation Database March 6, 2019, v2.1.1). The c.538C>T variant leads to a premature stop codon at position 180 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the GNAS gene are an established mechanism of disease in progressive osseous heteroplasia, Pseudohypoparathyroidism Ib, Pseudohypoparathyroidism Ia and is the type of variant expected to cause the disorder. However, the frequency of this loss of function variant is greater than expected for these conditions. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357204 SCV001552594 uncertain significance Pseudohypoparathyroidism type 1C no assertion criteria provided clinical testing The GNAS p.Q180* variant was identified in the literature in a cohort of 379,768 UK Biobank participants of European ancestry at a minor allele frequency of 0.03063 and was classified as a benign variant for albright hereditary osteodystrophy (Wright_2019_PMID_30665703). The variant was identified in dbSNP (ID: rs200910410) but was not identified in ClinVar. The variant was identified in control databases in 28 of 267434 chromosomes at a frequency of 0.0001047, where it was observed only in the European (non-Finnish) population in 28 of 121272 chromosomes (freq: 0.0002309) (Genome Aggregation Database March 6, 2019, v2.1.1). The c.538C>T variant leads to a premature stop codon at position 180 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the GNAS gene are an established mechanism of disease in progressive osseous heteroplasia, Pseudohypoparathyroidism Ib, Pseudohypoparathyroidism Ia and is the type of variant expected to cause the disorder. However, the frequency of this loss of function variant is greater than expected for these conditions. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001358585 SCV001554366 uncertain significance Pseudopseudohypoparathyroidism no assertion criteria provided clinical testing The GNAS p.Q180* variant was identified in the literature in a cohort of 379,768 UK Biobank participants of European ancestry at a minor allele frequency of 0.03063 and was classified as a benign variant for albright hereditary osteodystrophy (Wright_2019_PMID_30665703). The variant was identified in dbSNP (ID: rs200910410) but was not identified in ClinVar. The variant was identified in control databases in 28 of 267434 chromosomes at a frequency of 0.0001047, where it was observed only in the European (non-Finnish) population in 28 of 121272 chromosomes (freq: 0.0002309) (Genome Aggregation Database March 6, 2019, v2.1.1). The c.538C>T variant leads to a premature stop codon at position 180 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the GNAS gene are an established mechanism of disease in progressive osseous heteroplasia, Pseudohypoparathyroidism Ib, Pseudohypoparathyroidism Ia and is the type of variant expected to cause the disorder. However, the frequency of this loss of function variant is greater than expected for these conditions. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001358646 SCV001554440 uncertain significance Pseudohypoparathyroidism no assertion criteria provided clinical testing The GNAS p.Q180* variant was identified in the literature in a cohort of 379,768 UK Biobank participants of European ancestry at a minor allele frequency of 0.03063 and was classified as a benign variant for albright hereditary osteodystrophy (Wright_2019_PMID_30665703). The variant was identified in dbSNP (ID: rs200910410) but was not identified in ClinVar. The variant was identified in control databases in 28 of 267434 chromosomes at a frequency of 0.0001047, where it was observed only in the European (non-Finnish) population in 28 of 121272 chromosomes (freq: 0.0002309) (Genome Aggregation Database March 6, 2019, v2.1.1). The c.538C>T variant leads to a premature stop codon at position 180 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the GNAS gene are an established mechanism of disease in progressive osseous heteroplasia, Pseudohypoparathyroidism Ib, Pseudohypoparathyroidism Ia and is the type of variant expected to cause the disorder. However, the frequency of this loss of function variant is greater than expected for these conditions. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Clinical Genetics,Academic Medical Center RCV001698589 SCV001917030 uncertain significance not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV001698589 SCV001951138 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001698589 SCV001971780 uncertain significance not provided no assertion criteria provided clinical testing

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