rs2413739

Positions:

• chr22-43001030-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PACSIN2	NM_001184970.3	c.-78+13991G>A		intron_variant		ENST00000263246.8	NP_001171899.1
PACSIN2	NM_001349969.2	c.-78+13991G>A		intron_variant			NP_001336898.1
PACSIN2	NM_001349971.2	c.-78+13991G>A		intron_variant			NP_001336900.1
PACSIN2	NM_001349974.2	c.-64+13991G>A		intron_variant			NP_001336903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PACSIN2	ENST00000263246.8	c.-78+13991G>A		intron_variant		1	NM_001184970.3	ENSP00000263246	A1
PACSIN2	ENST00000422336.5	c.-78+1280G>A		intron_variant		5		ENSP00000403435
PACSIN2	ENST00000453643.5	c.-238-7250G>A		intron_variant		5		ENSP00000398573
PACSIN2	ENST00000445706.5	n.78+13991G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.0751

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.423

Alfa AF: 0.434 Hom.: 3657

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

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: rs2413739; hg19: chr22-43397036; COSMIC: COSV54322613;