3-64099131-G-C

Variant names:

• chr3-64099131-G-C
• rs972442832
• NM_198859.4:c.2455C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198859.4(PRICKLE2):​c.2455C>G​(p.Pro819Ala) 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. 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. P819S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRICKLE2 NM_198859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 0 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-AS1 (HGNC:):

PRICKLE2-AS1 (HGNC:40916): (PRICKLE2 antisense RNA 1)

ACMG classification

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=0.37368888).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	NM_198859.4	MANE Select	c.2455C>G	p.Pro819Ala	missense	Exon 8 of 8	NP_942559.1
	PRICKLE2	NM_001370528.1		c.2455C>G	p.Pro819Ala	missense	Exon 8 of 8	NP_001357457.1
	PRICKLE2-AS1	NR_045697.1		n.2505G>C		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	ENST00000638394.2	TSL:1 MANE Select	c.2455C>G	p.Pro819Ala	missense	Exon 8 of 8	ENSP00000492363.1
	PRICKLE2-AS1	ENST00000482609.1	TSL:1	n.2505G>C		non_coding_transcript_exon	Exon 3 of 3
	PRICKLE2	ENST00000295902.11	TSL:5	c.2623C>G	p.Pro875Ala	missense	Exon 9 of 9	ENSP00000295902.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Benign	0.84
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.045
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.8
PrimateAI	Uncertain	0.66	T
REVEL	Uncertain	0.49
Polyphen		0.33	B
MutPred		0.27		Loss of loop (P = 0.0288)
MVP		0.47
MPC		0.47
ClinPred		0.71	D
GERP RS		5.6
Varity_R		0.092
gMVP		0.45
Mutation Taster		=73/27	polymorphism

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: rs972442832; hg19: chr3-64084807;