Genetic Variant PRICKLE2:p.Asp272Glu (chr3-64147674-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_198859.4(PRICKLE2):c.816T>A(p.Asp272Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D272D) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRICKLE2
NM_198859.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.979

Publications

14 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

PRICKLE2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3809694).

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.816T>A	p.Asp272Glu	missense	Exon 7 of 8	NP_942559.1	Q7Z3G6
	PRICKLE2	NM_001370528.1		c.816T>A	p.Asp272Glu	missense	Exon 7 of 8	NP_001357457.1	Q7Z3G6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRICKLE2	ENST00000638394.2	TSL:1 MANE Select	c.816T>A	p.Asp272Glu	missense	Exon 7 of 8	ENSP00000492363.1	Q7Z3G6
PRICKLE2	ENST00000295902.11	TSL:5	c.984T>A	p.Asp328Glu	missense	Exon 8 of 9	ENSP00000295902.7	A0A1X7SBR1
PRICKLE2	ENST00000906078.1		c.816T>A	p.Asp272Glu	missense	Exon 7 of 9	ENSP00000576137.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1461586

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727108

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111998

Other (OTH)

AF:

0.00

AC:

AN:

60396

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

48653

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Benign

0.0090

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.25

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.83

M_CAP

Benign

0.046

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.65

PhyloP100

-0.98

PrimateAI

Pathogenic

0.84

REVEL

Uncertain

0.47

Polyphen

0.096

MutPred

0.33

Gain of disorder (P = 0.1563)

MVP

0.72

MPC

0.72

ClinPred

0.69

GERP RS

-7.5

Varity_R

0.11

gMVP

0.84

Mutation Taster

=72/28

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over