rs9386042

Variant names:

• chr6-143698317-T-C
• rs9386042
• NM_001100164.2:c.47-13699T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

PHACTR2 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PHACTR2	NM_001100164.2	c.47-13699T>C		intron_variant	Intron 1 of 12	ENST00000440869.7	NP_001093634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR2	ENST00000440869.7	c.47-13699T>C		intron_variant	Intron 1 of 12	2	NM_001100164.2	ENSP00000417038.2

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

African (AFR) AF: 0.239 AC: 9896 AN: 41480

American (AMR) AF: 0.185 AC: 2828 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3472

East Asian (EAS) AF: 0.362 AC: 1871 AN: 5168

South Asian (SAS) AF: 0.324 AC: 1561 AN: 4824

European-Finnish (FIN) AF: 0.241 AC: 2554 AN: 10580

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16959 AN: 67980

Other (OTH) AF: 0.239 AC: 502 AN: 2104

Alfa AF: 0.248 Hom.: 2809

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
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs9386042; hg19: chr6-144019454;