chr12-57544782-A-G

Variant names:

• chr12-57544782-A-G
• rs730560
• NM_001261413.2:c.105+1246T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001261413.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCTN2	NM_001261413.2	MANE Select	c.105+1246T>C		intron	N/A	NP_001248342.1
	DCTN2	NM_001348065.2		c.234+1246T>C		intron	N/A	NP_001334994.1
	DCTN2	NM_006400.5		c.105+1246T>C		intron	N/A	NP_006391.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCTN2	ENST00000548249.6	TSL:1 MANE Select	c.105+1246T>C		intron	N/A	ENSP00000447824.1
	DCTN2	ENST00000678990.1		n.1494T>C		non_coding_transcript_exon	Exon 2 of 2
	DCTN2	ENST00000434715.7	TSL:5	c.105+1246T>C		intron	N/A	ENSP00000408910.3

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

African (AFR) AF: 0.0987 AC: 4091 AN: 41440

American (AMR) AF: 0.384 AC: 5862 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1579 AN: 3466

East Asian (EAS) AF: 0.374 AC: 1929 AN: 5160

South Asian (SAS) AF: 0.300 AC: 1442 AN: 4812

European-Finnish (FIN) AF: 0.299 AC: 3152 AN: 10534

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.428 AC: 29096 AN: 67924

Other (OTH) AF: 0.362 AC: 763 AN: 2110

Alfa AF: 0.404 Hom.: 23007

Bravo AF: 0.315

Asia WGS AF: 0.306 AC: 1062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.73
PhyloP100		-0.26
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: rs730560; hg19: chr12-57938565;