ClinVar Miner

Submissions for variant NM_001875.5(CPS1):c.4101+2T>C (rs767575696)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668329 SCV000792908 likely pathogenic Congenital hyperammonemia, type I 2017-08-04 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000668329 SCV001337962 likely pathogenic Congenital hyperammonemia, type I 2020-01-19 criteria provided, single submitter clinical testing Variant summary: CPS1 c.4101+2T>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251366 control chromosomes. c.4101+2T>C has been reported in the literature in at-least two individuals affected with Carbamoylphosphate Synthetase I Deficiency from one family and expressing variable clinical severity (example, Haberle_2004, Klaus_2009). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
OMIM RCV000668329 SCV000044990 pathogenic Congenital hyperammonemia, type I 2009-09-01 no assertion criteria provided literature only

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