ClinVar Miner

Submissions for variant NM_032122.5(DTNBP1):c.667+2C>T

gnomAD frequency: 0.02578  dbSNP: rs61739410
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000219066 SCV000269042 benign not specified 2015-08-12 criteria provided, single submitter clinical testing c.667+2C>T in intron 8 of DTNBP1: This variant is not expected to have clinical significance because it has been identified in 8.9% (920/10324) of African chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs61739410).
Labcorp Genetics (formerly Invitae), Labcorp RCV000956367 SCV001103129 benign not provided 2025-01-30 criteria provided, single submitter clinical testing
GeneDx RCV000956367 SCV001827323 benign not provided 2018-10-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000219066 SCV002104022 benign not specified 2022-02-22 criteria provided, single submitter clinical testing Variant summary: DTNBP1 c.667+2C>T is located in a canonical splice-site. Several computational tools predict the variant strengthens/creates a canonical 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0073 in 251232 control chromosomes, predominantly at a frequency of 0.087 within the African or African-American subpopulation in the gnomAD database, including 75 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 550-fold of the estimated maximal expected allele frequency for a pathogenic variant in DTNBP1 causing Hermansky-Pudlak Syndrome phenotype (0.00016), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.667+2C>T in individuals affected with Hermansky-Pudlak Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign.

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