6-143714327-T-C

Variant names:

• chr6-143714327-T-C
• rs1015341
• NM_001100164.2:c.214+2144T>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+2144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,114 control chromosomes in the GnomAD database, including 17,555 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 0.48 (17555 hom., cov: 33)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.544 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+2144T>C		intron	N/A	NP_001093634.1
	PHACTR2	NM_014721.3		c.181+2144T>C		intron	N/A	NP_055536.2
	PHACTR2	NM_001394736.1		c.385+2144T>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+2144T>C		intron	N/A	ENSP00000417038.2
	PHACTR2	ENST00000427704.6	TSL:1	c.181+2144T>C		intron	N/A	ENSP00000391763.2
	PHACTR2	ENST00000367582.7	TSL:1	c.214+2144T>C		intron	N/A	ENSP00000356554.3

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72292 AN: 151996 Hom.: 17538 Cov.: 33

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.476 AC: 72358 AN: 152114 Hom.: 17555 Cov.: 33 AF XY: 0.474 AC XY: 35212 AN XY: 74360

African (AFR) AF: 0.397 AC: 16470 AN: 41500

American (AMR) AF: 0.446 AC: 6813 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1765 AN: 3470

East Asian (EAS) AF: 0.435 AC: 2251 AN: 5178

South Asian (SAS) AF: 0.562 AC: 2708 AN: 4820

European-Finnish (FIN) AF: 0.462 AC: 4879 AN: 10558

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35706 AN: 67984

Other (OTH) AF: 0.496 AC: 1048 AN: 2112

Alfa AF: 0.506 Hom.: 33718

Bravo AF: 0.466

Asia WGS AF: 0.552 AC: 1915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.60
PhyloP100		-0.53
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: rs1015341; hg19: chr6-144035464;