rs730560

Positions:

• chr12-57544782-A-G

Variant summary

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

The NM_001261413.2(DCTN2):​c.105+1246T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,918 control chromosomes in the GnomAD database, including 9,211 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 0.32 (9211 hom., cov: 31)
• Consequence: DCTN2 NM_001261413.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

Genes affected

DCTN2 (HGNC:2712): (dynactin subunit 2) This gene encodes a 50-kD subunit of dynactin, a macromolecular complex consisting of 10-11 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit is present in 4-5 copies per dynactin molecule. It contains three short alpha-helical coiled-coil domains that may mediate association with self or other dynactin subunits. It may interact directly with the largest subunit (p150) of dynactin and may affix p150 in place. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCTN2	NM_001261413.2	c.105+1246T>C		intron_variant		ENST00000548249.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCTN2	ENST00000548249.6	c.105+1246T>C		intron_variant		1	NM_001261413.2	P4

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48343 AN: 151800 Hom.: 9223 Cov.: 31

Gnomad AFR AF: 0.0990

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.318 AC: 48311 AN: 151918 Hom.: 9211 Cov.: 31 AF XY: 0.314 AC XY: 23305 AN XY: 74250

Gnomad4 AFR AF: 0.0987

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.362

Alfa AF: 0.416 Hom.: 15285

Bravo AF: 0.315

Asia WGS AF: 0.306 AC: 1062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.73

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: rs730560; hg19: chr12-57938565;