rs199566606

Variant names:

• chr3-64157308-C-G
• NM_198859.4:c.454G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-64157308-C-G
• chr3-64157308-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_198859.4(PRICKLE2):​c.454G>C​(p.Gly152Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: PRICKLE2 NM_198859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.02

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.892
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRICKLE2	NM_198859.4	c.454G>C	p.Gly152Arg	missense_variant	Exon 5 of 8	ENST00000638394.2	NP_942559.1
PRICKLE2	NM_001370528.1	c.454G>C	p.Gly152Arg	missense_variant	Exon 5 of 8		NP_001357457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.454G>C	p.Gly152Arg	missense_variant	Exon 5 of 8	1	NM_198859.4	ENSP00000492363.1
PRICKLE2	ENST00000295902.11	c.622G>C	p.Gly208Arg	missense_variant	Exon 6 of 9	5		ENSP00000295902.7
PRICKLE2	ENST00000564377.6	c.454G>C	p.Gly152Arg	missense_variant	Exon 5 of 8	5		ENSP00000455004.2
PRICKLE2	ENST00000640303.1	n.1093G>C		non_coding_transcript_exon_variant	Exon 3 of 6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461710 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 727158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.84	D;D;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Pathogenic	0.40	D
MetaRNN	Pathogenic	0.89	D;D;D
MetaSVM	Uncertain	0.67	D
MutationAssessor	Pathogenic	3.1	M;M;.
PrimateAI	Uncertain	0.76	T
REVEL	Uncertain	0.62
Polyphen		0.79	P;P;.
MutPred		0.73		Loss of catalytic residue at V153 (P = 0.0297);Loss of catalytic residue at V153 (P = 0.0297);.;
MVP		0.85
MPC		1.3
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.59
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-64142984;