ClinVar Miner

Submissions for variant NM_016341.4(PLCE1):c.1927G>T (p.Ala643Ser)

dbSNP: rs61886330
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000516190 SCV000614586 uncertain significance not specified 2016-12-28 criteria provided, single submitter clinical testing
Invitae RCV000891403 SCV001035219 likely benign not provided 2023-10-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001108876 SCV001266163 uncertain significance Nephrotic syndrome, type 3 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
PreventionGenetics, part of Exact Sciences RCV003900076 SCV004708779 likely benign PLCE1-related condition 2021-08-11 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000891403 SCV001552485 uncertain significance not provided no assertion criteria provided clinical testing The PLCE1 p.Ala643Ser variant was identified in the literature in 1 of 69 families with focal and segmental glomerulosclerosis (Gbadegesin_2009_PMID:18975016). The variant was identified in dbSNP (ID: rs61886330), ClinVar (classified as uncertain significance by Athena Diagnostics Inc) and LOVD 3.0 (classified as likely benign). The variant was identified in control databases in 383 of 280922 chromosomes (1 homozygous) at a frequency of 0.001363 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (Finnish) in 63 of 25038 chromosomes (freq: 0.002516), Other in 15 of 7146 chromosomes (freq: 0.002099), European (non-Finnish) in 270 of 128664 chromosomes (freq: 0.002098), South Asian in 16 of 30602 chromosomes (freq: 0.000523), Ashkenazi Jewish in 4 of 10360 chromosomes (freq: 0.000386), Latino in 13 of 35376 chromosomes (freq: 0.000368) and African in 2 of 24200 chromosomes (freq: 0.000083), but was not observed in the East Asian population. The p.Ala643 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of 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 the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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