chr6-15533238-G-A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 4P and 16B. PVS1_StrongBP6_Very_StrongBA1
The NM_032122.5(DTNBP1):c.667+2C>T variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,613,486 control chromosomes in the GnomAD database, including 286 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_032122.5 splice_donor
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DTNBP1 | NM_032122.5 | c.667+2C>T | splice_donor_variant | ENST00000344537.10 | NP_115498.2 | |||
LOC105374947 | XR_007059475.1 | n.6115G>A | non_coding_transcript_exon_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DTNBP1 | ENST00000344537.10 | c.667+2C>T | splice_donor_variant | 1 | NM_032122.5 | ENSP00000341680 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0239 AC: 3637AN: 152026Hom.: 147 Cov.: 31
GnomAD3 exomes AF: 0.00732 AC: 1838AN: 251232Hom.: 78 AF XY: 0.00554 AC XY: 752AN XY: 135808
GnomAD4 exome AF: 0.00273 AC: 3989AN: 1461344Hom.: 141 Cov.: 32 AF XY: 0.00254 AC XY: 1846AN XY: 726992
GnomAD4 genome AF: 0.0239 AC: 3636AN: 152142Hom.: 145 Cov.: 31 AF XY: 0.0234 AC XY: 1743AN XY: 74378
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 22, 2022 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 12, 2015 | 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). - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 27, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at