ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.8123C>T (p.Thr2708Met) (rs147350387)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000246229 SCV000305786 likely benign not specified criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000999995 SCV000604726 benign Polycystic kidney disease, adult type 2020-02-20 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000712656 SCV000843175 benign not provided 2018-07-17 criteria provided, single submitter clinical testing
Molecular Genetics of Inherited Kidney Disorders Laboratory,Garvan Institute of Medical Research RCV001254186 SCV001430207 likely benign Autosomal dominant polycystic kidney disease 2019-01-01 criteria provided, single submitter research
GeneDx RCV000712656 SCV001949023 benign not provided 2020-02-11 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 27499327, 24374109)
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001292087 SCV001480853 likely benign Polycystic kidney disease no assertion criteria provided clinical testing The PKD1 p.Thr2708Met variant was identified in 10 of 1016 proband chromosomes (frequency: 0.01) from individuals or families with ADPKD (classified as a polymorphism) and was not identified in 100 control chromosomes from healthy individuals (Bataille 2011, Garcia-Gonzalez 2007, Rossetti 2001, Rossetti 2012). This variant has been seen in one individual from our laboratory as co-occurring with a pathogenic variant increasing the likelihood it may not have clinical significance. The variant was also identified in dbSNP (ID: rs147350387) as “N/A”. The variant was identified in the 1000 Genomes Project in 20 of 5000 chromosomes (frequency: 0.004); in NHLBI GO Exome Sequencing Project in 129 of 8168 European American (frequency: 0.016) and 11 of 4082 African American (frequency: 0.0027) alleles. In the Exome Aggregation Consortium database (March 14, 2016) in 114 of 17104 chromosomes of which 1 was homozygous (frequency: 0.00666) in the following populations: 101 of 6264 European (Non-Finnish) – frequency 0.01612; 6 of 7956 South Asian- frequency 0.0007541; 3 of 490 Latinos- frequency 0.006122; 2 of 60 Finnish - frequency 0.03333; 1 of 1246 African - frequency 0.0008026 and 1 of 164 Other- frequency: 0.006098) alleles. The variant was identified in ADPKD Mutation Database classified as likely neutral. The p.Thr2708 residue is conserved across mammals and other organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) 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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