ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.735-10C>T (rs553975112)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001087418 SCV000554136 likely benign Peutz-Jeghers syndrome 2020-09-24 criteria provided, single submitter clinical testing
Color Health, Inc RCV000775656 SCV000910047 likely benign Hereditary cancer-predisposing syndrome 2017-11-26 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000461007 SCV001134848 benign not provided 2018-12-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192855 SCV001361277 likely benign not specified 2019-11-08 criteria provided, single submitter clinical testing Variant summary: STK11 c.735-10C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.4e-05 in 247506 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.735-10C>T in individuals affected with Peutz-Jeghers Syndrome 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. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354492 SCV001549123 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The STK11 c.735-10C>T variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (ID: rs553975112) as “With Likely benign allele” and ClinVar (classified as likely benign by Invitae and Color). The variant was identified in control databases in 5 of 245208 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: East Asian in 3 of 17232 chromosomes (freq: 0.0002, increasing the chances that this is a low frequency benign variant), European Non-Finnish in 1 of 111040 chromosomes (freq: 0.000009), and European Finnish in 1 of 22288 chromosomes (freq: 0.00005), while it was not observed in the African, Other, Latino, Ashkenazi Jewish, or South Asian populations. The c.735-10C>T variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions, although positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. However, 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, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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