chr3-64188225-T-C

Variant names:

• chr3-64188225-T-C
• rs1035275
• NM_198859.4:c.144+10559A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	NM_198859.4	MANE Select	c.144+10559A>G		intron	N/A	NP_942559.1
	PRICKLE2	NM_001370528.1		c.144+10559A>G		intron	N/A	NP_001357457.1
	PRICKLE2-AS3	NR_046702.1		n.62+620T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	ENST00000638394.2	TSL:1 MANE Select	c.144+10559A>G		intron	N/A	ENSP00000492363.1
	PRICKLE2	ENST00000295902.11	TSL:5	c.312+10559A>G		intron	N/A	ENSP00000295902.7
	PRICKLE2	ENST00000906078.1		c.144+10559A>G		intron	N/A	ENSP00000576137.1

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

African (AFR) AF: 0.129 AC: 5352 AN: 41560

American (AMR) AF: 0.462 AC: 7052 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3472

East Asian (EAS) AF: 0.259 AC: 1335 AN: 5160

South Asian (SAS) AF: 0.439 AC: 2114 AN: 4818

European-Finnish (FIN) AF: 0.522 AC: 5527 AN: 10584

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30512 AN: 67982

Other (OTH) AF: 0.388 AC: 819 AN: 2112

Alfa AF: 0.406 Hom.: 20203

Bravo AF: 0.344

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.22
DANN	Benign	0.73
PhyloP100		-1.9
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: rs1035275; hg19: chr3-64173901;