rs908754452

Positions:

• chr3-64147270-A-C
• chr3-64147270-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000638394.2(PRICKLE2):​c.1220T>G​(p.Met407Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M407T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRICKLE2 ENST00000638394.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.93

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13179395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRICKLE2	NM_198859.4	c.1220T>G	p.Met407Arg	missense_variant	7/8	ENST00000638394.2	NP_942559.1
PRICKLE2	NM_001370528.1	c.1220T>G	p.Met407Arg	missense_variant	7/8		NP_001357457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRICKLE2	ENST00000638394.2	c.1220T>G	p.Met407Arg	missense_variant	7/8	1	NM_198859.4	ENSP00000492363

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.093	T;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.052
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	.;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.58	N;N;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.62	.;N;.
REVEL	Benign	0.15
Sift	Benign	0.52	.;T;.
Polyphen		0.10	B;B;.
MutPred		0.18		Gain of methylation at K406 (P = 0.055);Gain of methylation at K406 (P = 0.055);.;
MVP		0.29
MPC		0.74
ClinPred		0.55	D
GERP RS		5.7
Varity_R		0.65
gMVP		0.40

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: rs908754452; hg19: chr3-64132946;