ClinVar Miner

Submissions for variant NM_015375.3(DSTYK):c.654+1G>A

gnomAD frequency: 0.00030  dbSNP: rs201091809
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001853078 SCV002192690 uncertain significance not provided 2022-03-04 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2 of the DSTYK gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in the loss of 9 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is present in population databases (rs201091809, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. Disruption of this splice site has been observed in individual(s) with congenital abnormalities of the kidney and urinary tract (PMID: 23862974). ClinVar contains an entry for this variant (Variation ID: 60684). Studies have shown that disruption of this splice site results in the activation of a cryptic splice site in exon 2 (PMID: 23862974). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL) RCV003387748 SCV003920758 pathogenic Hereditary spastic paraplegia 23 2023-04-27 criteria provided, single submitter research
OMIM RCV000054497 SCV000082975 uncertain significance Congenital anomalies of kidney and urinary tract 1 2013-08-15 no assertion criteria provided literature only
PreventionGenetics, part of Exact Sciences RCV003905015 SCV004726605 uncertain significance DSTYK-related disorder 2024-01-23 no assertion criteria provided clinical testing The DSTYK c.654+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was reported in at least seven individuals from a single family with renal hypodysplasia, ureteropelvic junction obstruction and vesicoureteral reflux, as well as two unaffected family members and several family members with unknown phenotype (Sanna-Cherchi et al 2013. PubMed ID: 23862974). This variant has also been reported in the heterozygous state in a patient with branchiootorenal syndrome features but normal renal ultrasound, and incomplete penetrance was suggested (Heidet et al 2017. PubMed ID: 28566479). This variant is reported in 0.081% of alleles in individuals of Latino descent in gnomAD. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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