3-64188225-T-C

Position:

• chr3-64188225-T-C

Variant summary

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

The NM_198859.4(PRICKLE2):​c.144+10559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,172 control chromosomes in the GnomAD database, including 11,585 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 0.36 (11585 hom., cov: 33)
• Consequence: PRICKLE2 NM_198859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

Genes affected

PRICKLE2 (HGNC:20340): (prickle planar cell polarity protein 2) This gene encodes a homolog of Drosophila prickle. The exact function of this gene is not known, however, studies in mice suggest that it may be involved in seizure prevention. Mutations in this gene are associated with progressive myoclonic epilepsy type 5. [provided by RefSeq, Dec 2011]

PRICKLE2-AS3 (HGNC:40918): (PRICKLE2 antisense RNA 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRICKLE2	NM_198859.4	c.144+10559A>G		intron_variant		ENST00000638394.2
PRICKLE2-AS3	NR_046702.1	n.62+620T>C		intron_variant, non_coding_transcript_variant
PRICKLE2	NM_001370528.1	c.144+10559A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.144+10559A>G		intron_variant		1	NM_198859.4
PRICKLE2-AS3	ENST00000473434.1	n.62+620T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54785 AN: 152052 Hom.: 11583 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.360 AC: 54791 AN: 152172 Hom.: 11585 Cov.: 33 AF XY: 0.366 AC XY: 27211 AN XY: 74394

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.388

Alfa AF: 0.417 Hom.: 2830

Bravo AF: 0.344

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.22
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: rs1035275; hg19: chr3-64173901;