rs34514

Positions:

• chr16-23659276-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032486.4(DCTN5):​c.236+651G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,066 control chromosomes in the GnomAD database, including 3,452 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 0.21 (3452 hom., cov: 32)
• Consequence: DCTN5 NM_032486.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTN5	NM_032486.4	c.236+651G>A		intron_variant		ENST00000300087.7	NP_115875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCTN5	ENST00000300087.7	c.236+651G>A		intron_variant		1	NM_032486.4	ENSP00000300087	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31478 AN: 151948 Hom.: 3454 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.207 AC: 31499 AN: 152066 Hom.: 3452 Cov.: 32 AF XY: 0.210 AC XY: 15636 AN XY: 74330

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.218

Alfa AF: 0.206 Hom.: 4424

Bravo AF: 0.199

Asia WGS AF: 0.293 AC: 1017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.7
DANN	Benign	0.71

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: rs34514; hg19: chr16-23670597;