rs12199775

Variant names:

• chr6-143577757-A-G
• rs12199775
• NM_001394736.1:c.217+40550A>G

Variant summary

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

The NM_001394736.1(PHACTR2):​c.217+40550A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 145,372 control chromosomes in the GnomAD database, including 244 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 0.049 (244 hom., cov: 31)
• Consequence: PHACTR2 NM_001394736.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581
• Publications: 31 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0695 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394736.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	NM_001394736.1		c.217+40550A>G		intron	N/A	NP_001381665.1	J3KP75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	ENST00000367584.8	TSL:5	c.217+40550A>G		intron	N/A	ENSP00000356556.4	J3KP75

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7108 AN: 145244 Hom.: 244 Cov.: 31

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0601

Gnomad AMR AF: 0.0392

Gnomad ASJ AF: 0.0408

Gnomad EAS AF: 0.0571

Gnomad SAS AF: 0.0761

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.0166

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.0455

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

GnomAD4 genome AF: 0.0489 AC: 7105 AN: 145372 Hom.: 244 Cov.: 31 AF XY: 0.0475 AC XY: 3364 AN XY: 70882

African (AFR) AF: 0.0105 AC: 412 AN: 39084

American (AMR) AF: 0.0390 AC: 568 AN: 14550

Ashkenazi Jewish (ASJ) AF: 0.0408 AC: 138 AN: 3382

East Asian (EAS) AF: 0.0571 AC: 294 AN: 5152

South Asian (SAS) AF: 0.0760 AC: 359 AN: 4724

European-Finnish (FIN) AF: 0.0592 AC: 590 AN: 9960

Middle Eastern (MID) AF: 0.0176 AC: 5 AN: 284

European-Non Finnish (NFE) AF: 0.0703 AC: 4597 AN: 65374

Other (OTH) AF: 0.0449 AC: 89 AN: 1980

Alfa AF: 0.0585 Hom.: 317

Bravo AF: 0.0433

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.71
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12199775; hg19: chr6-143898894;