ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2211-5T>G (rs368596736)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000588531 SCV000254402 likely benign not provided 2019-03-01 criteria provided, single submitter clinical testing
Counsyl RCV000409905 SCV000488293 uncertain significance Lynch syndrome I 2016-03-08 criteria provided, single submitter clinical testing
GeneDx RCV000588531 SCV000565201 uncertain significance not provided 2018-08-07 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.2211-5T>G or IVS13-5T>G and consists of a T>G nucleotide substitution at the -5 position of intron 13 of the MSH2 gene. In silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. MSH2 c.2211-5T>G has been observed in at least one individual with a personal history of Lynch syndrome-associated cancer and/or polyps (Yurgelun 2015). This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether MSH2 c.2211-5T>G is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000568854 SCV000662243 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000588531 SCV000696240 uncertain significance not provided 2017-01-16 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.2211-5T>G variant involves the alteration of a conserved intronic nucleotide, which 4/5 splice prediction tools predict an alteration to splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1/121160 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic MSH2 variant (0.0005683). This variant has been reported in one individual undergoing Lynch Syndrome testing. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/VUS. Taken together, this variant is classified as a Variant of Uncertain Significance, until more information becomes available.
Color RCV000568854 SCV000903117 likely benign Hereditary cancer-predisposing syndrome 2016-04-21 criteria provided, single submitter clinical testing

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