rs2413739

Variant names:

• chr22-43001030-C-T
• rs2413739
• NM_001184970.3:c.-78+13991G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184970.3(PACSIN2):​c.-78+13991G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,034 control chromosomes in the GnomAD database, including 14,360 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 0.43 (14360 hom., cov: 32)
• Consequence: PACSIN2 NM_001184970.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 20 publications found

Genes affected

PACSIN2 (HGNC:8571): (protein kinase C and casein kinase substrate in neurons 2) This gene is a member of the protein kinase C and casein kinase substrate in neurons family. The encoded protein is involved in linking the actin cytoskeleton with vesicle formation by regulating tubulin polymerization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PACSIN2	NM_001184970.3	c.-78+13991G>A		intron_variant	Intron 1 of 10	ENST00000263246.8	NP_001171899.1
PACSIN2	NM_001349969.2	c.-78+13991G>A		intron_variant	Intron 1 of 11		NP_001336898.1
PACSIN2	NM_001349971.2	c.-78+13991G>A		intron_variant	Intron 1 of 10		NP_001336900.1
PACSIN2	NM_001349974.2	c.-64+13991G>A		intron_variant	Intron 1 of 9		NP_001336903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PACSIN2	ENST00000263246.8	c.-78+13991G>A		intron_variant	Intron 1 of 10	1	NM_001184970.3	ENSP00000263246.3
PACSIN2	ENST00000453643.5	c.-238-7250G>A		intron_variant	Intron 1 of 4	5		ENSP00000398573.1
PACSIN2	ENST00000422336.5	c.-78+1280G>A		intron_variant	Intron 1 of 3	5		ENSP00000403435.1
PACSIN2	ENST00000445706.5	n.78+13991G>A		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64766 AN: 151916 Hom.: 14328 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.0755

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.427 AC: 64844 AN: 152034 Hom.: 14360 Cov.: 32 AF XY: 0.420 AC XY: 31235 AN XY: 74326

African (AFR) AF: 0.488 AC: 20228 AN: 41464

American (AMR) AF: 0.389 AC: 5938 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1279 AN: 3466

East Asian (EAS) AF: 0.0751 AC: 389 AN: 5180

South Asian (SAS) AF: 0.403 AC: 1944 AN: 4826

European-Finnish (FIN) AF: 0.350 AC: 3701 AN: 10566

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29914 AN: 67944

Other (OTH) AF: 0.423 AC: 894 AN: 2112

Alfa AF: 0.420 Hom.: 24630

Bravo AF: 0.427

Asia WGS AF: 0.290 AC: 1012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.67
PhyloP100		-0.054
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: rs2413739; hg19: chr22-43397036; COSMIC: COSV54322613;