ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.48A>G (p.Ala16=) (rs372736227)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000520646 SCV000616441 likely benign Rasopathy 2017-04-18 reviewed by expert panel curation The filtering allele frequency of the c.48A>G (p.Ala16=) variant in the PTPN11 gene is 0.0284% (9/16512) of South Asian chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BS1; PMID:29493581)
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000037648 SCV000061310 likely benign not specified 2014-11-10 criteria provided, single submitter clinical testing p.Ala16Ala in exon 2 of PTPN11: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 22/66740 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org/; dbSNP rs372736227).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000587695 SCV000227276 uncertain significance not provided 2014-12-10 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000359447 SCV000376314 benign Metachondromatosis 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000390713 SCV000376315 uncertain significance Noonan syndrome 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000305683 SCV000376316 benign LEOPARD syndrome 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587695 SCV000698077 benign not provided 2016-10-17 criteria provided, single submitter clinical testing Variant summary: The PTPN11 c.48A>G (p.Ala16Ala) variant causes a synonymous change with 4/5 splice prediction tools predict no significant impact on normal splicing and no alterations to ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 34/121402 (1/3570), which exceeds the estimated maximal expected allele frequency for a pathogenic PTPN11 variant of 1/16000, therefore, suggesting this variant is likely a benign polymorphism. In addition, a reputable clinical diagnostic laboratory cites the variant as "likely benign." Therefore, the variant of interest has been classified as Benign.
Invitae RCV000520646 SCV000776897 likely benign Rasopathy 2020-07-13 criteria provided, single submitter clinical testing

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