rs1015340

Variant names:

• chr6-143714220-C-T
• rs1015340
• NM_001100164.2:c.214+2037C>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+2037C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,034 control chromosomes in the GnomAD database, including 18,333 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 0.49 (18333 hom., cov: 32)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 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+2037C>T		intron	N/A	NP_001093634.1
	PHACTR2	NM_014721.3		c.181+2037C>T		intron	N/A	NP_055536.2
	PHACTR2	NM_001394736.1		c.385+2037C>T		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+2037C>T		intron	N/A	ENSP00000417038.2
	PHACTR2	ENST00000427704.6	TSL:1	c.181+2037C>T		intron	N/A	ENSP00000391763.2
	PHACTR2	ENST00000367582.7	TSL:1	c.214+2037C>T		intron	N/A	ENSP00000356554.3

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74066 AN: 151916 Hom.: 18309 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.488 AC: 74141 AN: 152034 Hom.: 18333 Cov.: 32 AF XY: 0.485 AC XY: 36045 AN XY: 74310

African (AFR) AF: 0.444 AC: 18422 AN: 41476

American (AMR) AF: 0.446 AC: 6807 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1782 AN: 3470

East Asian (EAS) AF: 0.434 AC: 2242 AN: 5168

South Asian (SAS) AF: 0.560 AC: 2695 AN: 4812

European-Finnish (FIN) AF: 0.461 AC: 4872 AN: 10558

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35563 AN: 67976

Other (OTH) AF: 0.499 AC: 1050 AN: 2106

Alfa AF: 0.508 Hom.: 75326

Bravo AF: 0.479

Asia WGS AF: 0.548 AC: 1904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.44
PhyloP100		-0.55
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: rs1015340; hg19: chr6-144035357;