Submissions for variant NM_007373.4(SHOC2):c.*16C>A

gnomAD frequency: 0.00013  dbSNP: rs753327392

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000423318	SCV000514628	benign	not specified	2015-05-21	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina	RCV001106769	SCV001263865	benign	Noonan syndrome-like disorder with loose anagen hair 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	RCV000423318	SCV001623385	benign	not specified	2021-04-26	criteria provided, single submitter	clinical testing	Variant summary: SHOC2 c.*16C>A is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.0001 in 250898 control chromosomes, predominantly at a frequency of 0.0006 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 24 fold of the estimated maximal expected allele frequency for a pathogenic variant in SHOC2 causing Noonan Syndrome with Loose Anagen Hair phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism. To our knowledge, no occurrence of c.*16C>A in individuals affected with Noonan Syndrome with Loose Anagen Hair and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both of them classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.