rs9403521

chr6-143673062-T-Cchr6-143673062-T-G

Variant summary

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

The ENST00000427704.6(PHACTR2):c.14-38954T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,046 control chromosomes in the GnomAD database, including 2,146 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 0.16 (2146 hom., cov: 31)
• Consequence: PHACTR2 ENST00000427704.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR2	NM_001100166.2	c.14-38954T>C		intron_variant
PHACTR2	NM_001394736.1	c.218-38954T>C		intron_variant
PHACTR2	NM_001394738.1	c.14-38954T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR2	ENST00000427704.6	c.14-38954T>C		intron_variant		1
PHACTR2	ENST00000305766.10	c.14-38954T>C		intron_variant		2
PHACTR2	ENST00000367584.8	c.218-38954T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24644 AN: 151928 Hom.: 2146 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.162 AC: 24661 AN: 152046 Hom.: 2146 Cov.: 31 AF XY: 0.167 AC XY: 12412 AN XY: 74316

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.156

Alfa AF: 0.149 Hom.: 1693

Bravo AF: 0.155

Asia WGS AF: 0.327 AC: 1133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.1
Dann	Benign	0.43

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: rs9403521; hg19: chr6-143994199;