rs9386042

Positions:

• chr6-143698317-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100164.2(PHACTR2):​c.47-13699T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,100 control chromosomes in the GnomAD database, including 4,598 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4598 hom., cov: 32)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161

Genes affected

PHACTR2 (HGNC:20956): (phosphatase and actin regulator 2) Predicted to enable actin binding activity. Predicted to be involved in actin cytoskeleton organization. Predicted to be located in plasma membrane and platelet alpha granule membrane. Implicated in Parkinson's disease and multiple sclerosis. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR2	NM_001100164.2	c.47-13699T>C		intron_variant		ENST00000440869.7	NP_001093634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR2	ENST00000440869.7	c.47-13699T>C		intron_variant		2	NM_001100164.2	ENSP00000417038	A1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37052 AN: 151982 Hom.: 4595 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.237

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.244 AC: 37081 AN: 152100 Hom.: 4598 Cov.: 32 AF XY: 0.245 AC XY: 18241 AN XY: 74352

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.239

Alfa AF: 0.248 Hom.: 2572

Bravo AF: 0.234

Asia WGS AF: 0.340 AC: 1177 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs9386042; hg19: chr6-144019454;