rs2619545

Variant names:

• chr6-15632510-T-C
• rs2619545
• NM_032122.5:c.223-5035A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032122.5(DTNBP1):​c.223-5035A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,004 control chromosomes in the GnomAD database, including 5,713 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5713 hom., cov: 32)
• Consequence: DTNBP1 NM_032122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 3 publications found

Genes affected

DTNBP1 (HGNC:17328): (dystrobrevin binding protein 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. A similar protein in mouse is a component of a protein complex termed biogenesis of lysosome-related organelles complex 1 (BLOC-1), and binds to alpha- and beta-dystrobrevins, which are components of the dystrophin-associated protein complex (DPC). Mutations in this gene are associated with Hermansky-Pudlak syndrome type 7. This gene may also be associated with schizophrenia. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DTNBP1 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNBP1	NM_032122.5	c.223-5035A>G		intron_variant	Intron 4 of 9	ENST00000344537.10	NP_115498.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNBP1	ENST00000344537.10	c.223-5035A>G		intron_variant	Intron 4 of 9	1	NM_032122.5	ENSP00000341680.6

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38787 AN: 151888 Hom.: 5707 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0953

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.255 AC: 38834 AN: 152004 Hom.: 5713 Cov.: 32 AF XY: 0.253 AC XY: 18802 AN XY: 74308

African (AFR) AF: 0.399 AC: 16538 AN: 41418

American (AMR) AF: 0.213 AC: 3260 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3472

East Asian (EAS) AF: 0.0957 AC: 495 AN: 5174

South Asian (SAS) AF: 0.206 AC: 995 AN: 4822

European-Finnish (FIN) AF: 0.218 AC: 2301 AN: 10556

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13903 AN: 67970

Other (OTH) AF: 0.238 AC: 504 AN: 2114

Alfa AF: 0.227 Hom.: 697

Bravo AF: 0.261

Asia WGS AF: 0.173 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.74
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2619545; hg19: chr6-15632741;