rs738536

Positions:

• chr22-42864421-G-A

Variant summary

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

The ENST00000507586.1(PACSIN2):​c.72-5899C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,014 control chromosomes in the GnomAD database, including 14,799 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 (14799 hom., cov: 32)
• Consequence: PACSIN2 ENST00000507586.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PACSIN2	ENST00000507586.1	c.72-5899C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65795 AN: 151896 Hom.: 14778 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.0954

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.433 AC: 65845 AN: 152014 Hom.: 14799 Cov.: 32 AF XY: 0.427 AC XY: 31709 AN XY: 74292

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.0947

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.442

Alfa AF: 0.472 Hom.: 18055

Bravo AF: 0.432

Asia WGS AF: 0.275 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.49
DANN	Benign	0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs738536; hg19: chr22-43260427;