rs9403521

Variant names:

• chr6-143673062-T-C
• rs9403521
• ENST00000427704.6:c.14-38954T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-143673062-T-C
• chr6-143673062-T-G

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.87).
• 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 rank	MANE	Protein	UniProt
PHACTR2	NM_014721.3	c.14-38954T>C		intron_variant	Intron 1 of 12		NP_055536.2
PHACTR2	NM_001394736.1	c.218-38954T>C		intron_variant	Intron 1 of 11		NP_001381665.1
PHACTR2	NM_001100166.2	c.14-38954T>C		intron_variant	Intron 1 of 11		NP_001093636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR2	ENST00000427704.6	c.14-38954T>C		intron_variant	Intron 1 of 12	1		ENSP00000391763.2
PHACTR2	ENST00000367584.8	c.218-38954T>C		intron_variant	Intron 1 of 11	5		ENSP00000356556.4
PHACTR2	ENST00000305766.10	c.14-38954T>C		intron_variant	Intron 1 of 11	2		ENSP00000305530.6

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

African (AFR) AF: 0.113 AC: 4700 AN: 41472

American (AMR) AF: 0.164 AC: 2509 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3468

East Asian (EAS) AF: 0.349 AC: 1799 AN: 5158

South Asian (SAS) AF: 0.276 AC: 1326 AN: 4804

European-Finnish (FIN) AF: 0.196 AC: 2068 AN: 10570

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11256 AN: 67986

Other (OTH) AF: 0.156 AC: 330 AN: 2110

Alfa AF: 0.153 Hom.: 2685

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
PhyloP100		0.40
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: rs9403521; hg19: chr6-143994199;