Genetic Variant DTNBP1:c.57-4699C>A (chr6-15656839-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is The variant received -2 classification points (ACMG Germline Pathogenicity v2019): 2P and 4B. PM2BP4_Strong

The NM_032122.5(DTNBP1):c.57-4699C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

DTNBP1
NM_032122.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

45 publications found

Variant links:

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: ClinGen, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)

DTNBP1 links:

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new If you want to explore the variant's impact on the transcript NM_032122.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 points.

PM2

Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: AR) (threshold 0.001) — PM2 moderate.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_032122.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DTNBP1	NM_032122.5	MANE Select	c.57-4699C>A	intron	N/A	NP_115498.2
DTNBP1	NM_001271668.2		c.57-4699C>A	intron	N/A	NP_001258597.1	A6NFV8
DTNBP1	NM_001271669.2		c.56+5975C>A	intron	N/A	NP_001258598.1	A0A087WYP9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DTNBP1	ENST00000344537.10	TSL:1 MANE Select	c.57-4699C>A	intron	N/A	ENSP00000341680.6	Q96EV8-1
DTNBP1	ENST00000622898.4	TSL:1	c.56+5975C>A	intron	N/A	ENSP00000481997.1	A0A087WYP9
DTNBP1	ENST00000338950.9	TSL:1	c.57-4699C>A	intron	N/A	ENSP00000344718.5	Q96EV8-2

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

502

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.016

(source)

DANN

Benign

0.62

PhyloP100

-1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over