ClinVar Miner

Submissions for variant NM_001128840.3(CACNA1D):c.5767_5769del (p.Phe1923del) (rs72556363)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000221136 SCV000270013 benign not specified 2016-08-09 criteria provided, single submitter clinical testing p.Phe1943del in exon 47 of CACNA1D: This variant is not expected to have clinica l significance because it has been identified in 0.4% (285/66318) of European ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs72556363).
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000442689 SCV000511353 likely benign not provided 2016-12-07 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Invitae RCV000442689 SCV001111672 likely benign not provided 2019-09-26 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000442689 SCV001143461 benign not provided 2019-07-12 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000442689 SCV001553343 likely benign not provided no assertion criteria provided clinical testing The CACNA1D p.Phe1923del variant was not identified in the literature nor was it identified in LOVD 3.0. The variant was identified in dbSNP (ID: rs72556363) and ClinVar (classified as likely benign by Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics and as benign by Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine). The variant was identified in control databases in 673 of 278936 chromosomes (3 homozygous) at a frequency of 0.002413 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 (non-Finnish) in 588 of 129052 chromosomes (freq: 0.004556), Other in 15 of 7200 chromosomes (freq: 0.002083), European (Finnish) in 20 of 21356 chromosomes (freq: 0.000937), African in 21 of 24966 chromosomes (freq: 0.000841), Latino in 24 of 35436 chromosomes (freq: 0.000677), Ashkenazi Jewish in 2 of 10368 chromosomes (freq: 0.000193) and South Asian in 3 of 30616 chromosomes (freq: 0.000098), but was not observed in the East Asian population. This variant is an in-frame deletion resulting in the removal of a phenylalanine (phe) residue at codon 1923; the impact of this alteration on CACNA1D protein function is not known. The variant occurs outside of the splicing consensus sequence and three of four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. 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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