rs11155313

Variant names:

• chr6-143640440-A-G
• rs11155313
• ENST00000427704.6:c.13+32118A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000427704.6(PHACTR2):​c.13+32118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,084 control chromosomes in the GnomAD database, including 6,595 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 0.29 (6595 hom., cov: 32)
• Consequence: PHACTR2 ENST00000427704.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.802
• Publications: 7 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427704.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	NM_014721.3		c.13+32118A>G		intron	N/A	NP_055536.2
	PHACTR2	NM_001394736.1		c.218-71576A>G		intron	N/A	NP_001381665.1
	PHACTR2	NM_001100166.2		c.13+32118A>G		intron	N/A	NP_001093636.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	ENST00000427704.6	TSL:1	c.13+32118A>G		intron	N/A	ENSP00000391763.2
	PHACTR2	ENST00000367584.8	TSL:5	c.218-71576A>G		intron	N/A	ENSP00000356556.4
	PHACTR2	ENST00000305766.10	TSL:2	c.13+32118A>G		intron	N/A	ENSP00000305530.6

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44667 AN: 151966 Hom.: 6588 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.294 AC: 44703 AN: 152084 Hom.: 6595 Cov.: 32 AF XY: 0.291 AC XY: 21606 AN XY: 74368

African (AFR) AF: 0.278 AC: 11524 AN: 41494

American (AMR) AF: 0.247 AC: 3773 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3470

East Asian (EAS) AF: 0.174 AC: 899 AN: 5170

South Asian (SAS) AF: 0.332 AC: 1597 AN: 4814

European-Finnish (FIN) AF: 0.261 AC: 2764 AN: 10574

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.323 AC: 21952 AN: 67962

Other (OTH) AF: 0.315 AC: 665 AN: 2112

Alfa AF: 0.261 Hom.: 1935

Bravo AF: 0.285

Asia WGS AF: 0.249 AC: 864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.71
PhyloP100		0.80
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: rs11155313; hg19: chr6-143961577; COSMIC: COSV59851812;