NM_198859.4:c.144+10T>C

Variant names:

• chr3-64198774-A-G
• rs74535153
• NM_198859.4:c.144+10T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_198859.4(PRICKLE2):​c.144+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,614,030 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (18 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (13 hom.)
• Consequence: PRICKLE2 NM_198859.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.810
• 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-AS3 (HGNC:40918): (PRICKLE2 antisense RNA 3)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-64198774-A-G is Benign according to our data. Variant chr3-64198774-A-G is described in ClinVar as Benign. ClinVar VariationId is 130031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00734 (1118/152292) while in subpopulation AFR AF = 0.0255 (1060/41554). AF 95% confidence interval is 0.0242. There are 18 homozygotes in GnomAd4. There are 535 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AD,AR gene

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.144+10T>C		intron	N/A	NP_942559.1
	PRICKLE2	NM_001370528.1		c.144+10T>C		intron	N/A	NP_001357457.1
	PRICKLE2-AS3	NR_046702.1		n.305A>G		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRICKLE2	ENST00000638394.2	TSL:1 MANE Select	c.144+10T>C		intron	N/A	ENSP00000492363.1
	PRICKLE2	ENST00000295902.11	TSL:5	c.312+10T>C		intron	N/A	ENSP00000295902.7
	PRICKLE2	ENST00000906078.1		c.144+10T>C		intron	N/A	ENSP00000576137.1

Frequencies

GnomAD3 genomes AF: 0.00727 AC: 1106 AN: 152174 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00200 AC: 503 AN: 251340 AF XY: 0.00145

Gnomad AFR exome AF: 0.0258

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000838 AC: 1225 AN: 1461738 Hom.: 13 Cov.: 32 AF XY: 0.000800 AC XY: 582 AN XY: 727184

African (AFR) AF: 0.0269 AC: 901 AN: 33476

American (AMR) AF: 0.00119 AC: 53 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00264 AC: 69 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00158 AC: 9 AN: 5714

European-Non Finnish (NFE) AF: 0.0000657 AC: 73 AN: 1111934

Other (OTH) AF: 0.00190 AC: 115 AN: 60384

GnomAD4 genome AF: 0.00734 AC: 1118 AN: 152292 Hom.: 18 Cov.: 32 AF XY: 0.00718 AC XY: 535 AN XY: 74474

African (AFR) AF: 0.0255 AC: 1060 AN: 41554

American (AMR) AF: 0.00209 AC: 32 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68024

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00578 Hom.: 4

Bravo AF: 0.00844

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Progressive myoclonic epilepsy type 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.62
PhyloP100		0.81
Mutation Taster		=100/0	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: rs74535153; hg19: chr3-64184450;