ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.1932C>G (p.Asp644Glu)

gnomAD frequency: 0.00041  dbSNP: rs80214209
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001084210 SCV000287541 benign Colorectal cancer, susceptibility to, 10 2024-01-30 criteria provided, single submitter clinical testing
GeneDx RCV000759222 SCV000520581 likely benign not provided 2021-01-25 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28944914)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000436158 SCV000888442 benign not specified 2017-11-22 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000436158 SCV002551941 benign not specified 2023-08-15 criteria provided, single submitter clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV001084210 SCV004016663 benign Colorectal cancer, susceptibility to, 10 2023-07-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000436158 SCV004029434 likely benign not specified 2023-07-04 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000759222 SCV005074640 likely benign not provided 2024-06-01 criteria provided, single submitter clinical testing POLD1: BS1
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000436158 SCV001550412 benign not specified no assertion criteria provided clinical testing The POLD1 p.Asp644Glu variant was identified in the literature in a case report in a patient with Hutchinson-Gilford progeria syndrome (Duan 2016). The variant was also identified in dbSNP (ID: rs80214209) as "With Likely benign allele", and in ClinVar database (classified as benign by Invitae; as likely benign by GeneDx and one clinical laboratory). The variant was not identified in Cosmic, or MutDB databases. The variant was identified in control databases in 204 of 276956 chromosomes (2 homozygous) at a frequency of 0.0007 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 3 of 6458 chromosomes (freq: 0.0005), Latino in 1 of 34414 chromosomes (freq: 0.00003), East Asian in 192 of 18864 chromosomes (freq: 0.01), and South Asian in 8 of 30780 chromosomes (freq: 0.0003), while the variant was not observed in the African, European, Ashkenazi Jewish, or Finnish populations. The p.Asp644 residue is conserved in mammals but not in more distantly related organisms however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 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 this variant meets our laboratory's criteria to be classified as benign.

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