chr3-64190833-C-G

Variant names:

• chr3-64190833-C-G
• rs153726
• NM_198859.4:c.144+7951G>C

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+7951G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,160 control chromosomes in the GnomAD database, including 3,286 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 0.19 (3286 hom., cov: 32)
• Consequence: PRICKLE2 NM_198859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRICKLE2	NM_198859.4	c.144+7951G>C		intron_variant	Intron 2 of 7	ENST00000638394.2	NP_942559.1
PRICKLE2	NM_001370528.1	c.144+7951G>C		intron_variant	Intron 2 of 7		NP_001357457.1
PRICKLE2-AS3	NR_046702.1	n.116+486C>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.144+7951G>C		intron_variant	Intron 2 of 7	1	NM_198859.4	ENSP00000492363.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29103 AN: 152040 Hom.: 3278 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.191 AC: 29126 AN: 152160 Hom.: 3286 Cov.: 32 AF XY: 0.190 AC XY: 14133 AN XY: 74416

African (AFR) AF: 0.264 AC: 10938 AN: 41506

American (AMR) AF: 0.185 AC: 2823 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3470

East Asian (EAS) AF: 0.480 AC: 2479 AN: 5160

South Asian (SAS) AF: 0.215 AC: 1037 AN: 4814

European-Finnish (FIN) AF: 0.0906 AC: 962 AN: 10616

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9635 AN: 67998

Other (OTH) AF: 0.188 AC: 397 AN: 2108

Alfa AF: 0.0446 Hom.: 34

Bravo AF: 0.204

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.93
DANN	Benign	0.69
PhyloP100		-0.45
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: rs153726; hg19: chr3-64176509;