rs12199775

Positions:

• chr6-143577757-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR2	NM_001394736.1	c.217+40550A>G		intron_variant			NP_001381665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR2	ENST00000367584.8	c.217+40550A>G		intron_variant		5		ENSP00000356556

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

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.0390

Gnomad4 ASJ AF: 0.0408

Gnomad4 EAS AF: 0.0571

Gnomad4 SAS AF: 0.0760

Gnomad4 FIN AF: 0.0592

Gnomad4 NFE AF: 0.0703

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0616 Hom.: 252

Bravo AF: 0.0433

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12199775; hg19: chr6-143898894;