chr6-143720985-T-C

Variant names:

• chr6-143720985-T-C
• rs6570578
• NM_001100164.2:c.214+8802T>C

Variant summary

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

The NM_001100164.2(PHACTR2):​c.214+8802T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,106 control chromosomes in the GnomAD database, including 30,415 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 0.62 (30415 hom., cov: 32)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100164.2. 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_001100164.2	MANE Select	c.214+8802T>C		intron	N/A	NP_001093634.1
	PHACTR2	NM_014721.3		c.181+8802T>C		intron	N/A	NP_055536.2
	PHACTR2	NM_001394736.1		c.385+8802T>C		intron	N/A	NP_001381665.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	ENST00000440869.7	TSL:2 MANE Select	c.214+8802T>C		intron	N/A	ENSP00000417038.2
	PHACTR2	ENST00000427704.6	TSL:1	c.181+8802T>C		intron	N/A	ENSP00000391763.2
	PHACTR2	ENST00000367582.7	TSL:1	c.214+8802T>C		intron	N/A	ENSP00000356554.3

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93587 AN: 151988 Hom.: 30363 Cov.: 32

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.616 AC: 93703 AN: 152106 Hom.: 30415 Cov.: 32 AF XY: 0.609 AC XY: 45274 AN XY: 74352

African (AFR) AF: 0.836 AC: 34676 AN: 41502

American (AMR) AF: 0.498 AC: 7609 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1872 AN: 3470

East Asian (EAS) AF: 0.510 AC: 2645 AN: 5186

South Asian (SAS) AF: 0.579 AC: 2791 AN: 4822

European-Finnish (FIN) AF: 0.478 AC: 5040 AN: 10554

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37057 AN: 67972

Other (OTH) AF: 0.602 AC: 1270 AN: 2110

Alfa AF: 0.569 Hom.: 9953

Bravo AF: 0.624

Asia WGS AF: 0.609 AC: 2114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.8
DANN	Benign	0.55
PhyloP100		-0.62
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: rs6570578; hg19: chr6-144042122;