6-143720567-G-T

Variant names:

• chr6-143720567-G-T
• rs6915752
• NM_001100164.2:c.214+8384G>T

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+8384G>T 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 152,030 control chromosomes in the GnomAD database, including 30,382 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 (30382 hom., cov: 31)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 3 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	NM_001100164.2	MANE Select	c.214+8384G>T		intron	N/A	NP_001093634.1	O75167-4
	PHACTR2	NM_014721.3		c.181+8384G>T		intron	N/A	NP_055536.2	O75167-1
	PHACTR2	NM_001394736.1		c.385+8384G>T		intron	N/A	NP_001381665.1	J3KP75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	ENST00000440869.7	TSL:2 MANE Select	c.214+8384G>T		intron	N/A	ENSP00000417038.2	O75167-4
	PHACTR2	ENST00000427704.6	TSL:1	c.181+8384G>T		intron	N/A	ENSP00000391763.2	O75167-1
	PHACTR2	ENST00000367582.7	TSL:1	c.214+8384G>T		intron	N/A	ENSP00000356554.3	O75167-2

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93500 AN: 151912 Hom.: 30330 Cov.: 31

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.502

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: 93616 AN: 152030 Hom.: 30382 Cov.: 31 AF XY: 0.609 AC XY: 45232 AN XY: 74314

African (AFR) AF: 0.836 AC: 34662 AN: 41472

American (AMR) AF: 0.497 AC: 7596 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1874 AN: 3468

East Asian (EAS) AF: 0.502 AC: 2588 AN: 5158

South Asian (SAS) AF: 0.579 AC: 2789 AN: 4818

European-Finnish (FIN) AF: 0.478 AC: 5047 AN: 10564

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

European-Non Finnish (NFE) AF: 0.545 AC: 37048 AN: 67958

Other (OTH) AF: 0.602 AC: 1273 AN: 2114

Alfa AF: 0.562 Hom.: 76098

Bravo AF: 0.623

Asia WGS AF: 0.607 AC: 2110 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	1.4
DANN	Benign	0.39
PhyloP100		0.0060
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: rs6915752; hg19: chr6-144041704;