16-23641699-A-G

Position:

• chr16-23641699-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032486.4(DCTN5):​c.48+109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 1,176,184 control chromosomes in the GnomAD database, including 2,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (1065 hom., cov: 32)
  • Exomes 𝑓: 0.050 (1862 hom.)
• Consequence: DCTN5 NM_032486.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.203

Genes affected

DCTN5 (HGNC:24594): (dynactin subunit 5) This gene encodes a subunit of dynactin, a component of the cytoplasmic dynein motor machinery involved in minus-end-directed transport. The encoded protein is a component of the pointed-end subcomplex and is thought to bind membranous cargo. A pseudogene of this gene is located on the long arm of chromosome 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

DCTN5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-23641699-A-G is Benign according to our data. Variant chr16-23641699-A-G is described in ClinVar as [Benign]. Clinvar id is 1236229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTN5	NM_032486.4	c.48+109A>G		intron_variant		ENST00000300087.7	NP_115875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCTN5	ENST00000300087.7	c.48+109A>G		intron_variant		1	NM_032486.4	ENSP00000300087.2

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14170 AN: 151820 Hom.: 1050 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.00947

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0440

Gnomad OTH AF: 0.0900

GnomAD4 exome AF: 0.0501 AC: 51335 AN: 1024246 Hom.: 1862 AF XY: 0.0499 AC XY: 26033 AN XY: 522068

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.0580

Gnomad4 EAS exome AF: 0.00821

Gnomad4 SAS exome AF: 0.0603

Gnomad4 FIN exome AF: 0.0392

Gnomad4 NFE exome AF: 0.0429

Gnomad4 OTH exome AF: 0.0624

GnomAD4 genome AF: 0.0937 AC: 14237 AN: 151938 Hom.: 1065 Cov.: 32 AF XY: 0.0938 AC XY: 6967 AN XY: 74304

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0631

Gnomad4 EAS AF: 0.00949

Gnomad4 SAS AF: 0.0629

Gnomad4 FIN AF: 0.0378

Gnomad4 NFE AF: 0.0440

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.0512 Hom.: 585

Bravo AF: 0.102

Asia WGS AF: 0.0820 AC: 288 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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

Publications

LitVar

Other links and lift over

dbSNP: rs8058061; hg19: chr16-23653020;