ClinVar Miner

Submissions for variant NM_013382.5(POMT2):c.924-2A>C (rs886044256)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523465 SCV000617439 pathogenic not provided 2016-06-08 criteria provided, single submitter clinical testing The c.924-2 A>C pathogenic splice site variant has been previously reported as a homozygous variant in three fetus' with congenital hydrocephalus in one consanguineous family (Abumansour et al., 2015). This variant destroys the canonical splice acceptor site of intron 7. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subjected to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.924-2 A>C variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret c.924-2 A>C as a pathogenic variant.
Invitae RCV000822848 SCV000963667 pathogenic Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A2; Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B2; Limb-girdle muscular dystrophy-dystroglycanopathy, type C2 2019-05-13 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 7 of the POMT2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in several individuals affected with POMT2-related Walker-Warburg Syndrome or POMT2-related lissencephaly (PMID: 18752264, 26495167, 17559086). ClinVar contains an entry for this variant (Variation ID: 449378). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in POMT2 are known to be pathogenic (PMID: 15894594). For these reasons, this variant has been classified as Pathogenic.

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