rs9390123

chr6-143622177-T-C

Variant summary

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

The ENST00000427704.6(PHACTR2):c.13+13855T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,920 control chromosomes in the GnomAD database, including 27,477 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 0.60 (27477 hom., cov: 31)
• Consequence: PHACTR2 ENST00000427704.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR2	NM_001100166.2	c.13+13855T>C		intron_variant
PHACTR2	NM_001394736.1	c.217+84970T>C		intron_variant
PHACTR2	NM_001394738.1	c.13+13855T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR2	ENST00000427704.6	c.13+13855T>C		intron_variant		1
PHACTR2	ENST00000305766.10	c.13+13855T>C		intron_variant		2
PHACTR2	ENST00000367584.8	c.217+84970T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90898 AN: 151802 Hom.: 27438 Cov.: 31

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.599 AC: 90991 AN: 151920 Hom.: 27477 Cov.: 31 AF XY: 0.597 AC XY: 44301 AN XY: 74236

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.594

Alfa AF: 0.600 Hom.: 39789

Bravo AF: 0.597

Asia WGS AF: 0.477 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.24
Dann	Benign	0.32

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: rs9390123; hg19: chr6-143943314;