ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.676-5T>C (rs200537780)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001507250 SCV000166532 benign Juvenile polyposis syndrome 2020-12-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131998 SCV000187057 likely benign Hereditary cancer-predisposing syndrome 2019-02-04 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Illumina Clinical Services Laboratory,Illumina RCV000123226 SCV000365648 benign Generalized juvenile polyposis/juvenile polyposis coli 2018-01-12 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.
Color Health, Inc RCV000131998 SCV000910562 benign Hereditary cancer-predisposing syndrome 2016-05-16 criteria provided, single submitter clinical testing
GeneDx RCV001668280 SCV001890858 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000582818 SCV000691801 likely benign not specified no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354511 SCV001549148 benign Hereditary mixed polyposis syndrome 2 no assertion criteria provided clinical testing The BMPR1A c.676-5T>C variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (rs200537780) as “with likely benign allele” and ClinVar (interpreted as "likely benign" by Ambry Genetics and 2 others and "benign" by Color and 1 other). The variant was identified in control databases in 567 of 276,986 chromosomes (8 homozygous) at a frequency of 0.002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 11 of 6458 chromosomes (freq: 0.002), European in 3 of 126,514 chromosomes (freq: 0.00002), and South Asian in 553 of 30,768 chromosomes (freq: 0.02). The variant was not observed in the African, Latino, Ashkenazi Jewish, East Asian and Finnish populations. In our laboratory, the variant was observed in an individual with a pathogenic CHEK2 variant (p.Gln20*). The c.676-5T>C variant is located at a non-conserved nucleotide in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.

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