ENST00000427704.6:c.13+13855T>C

Variant names:

• chr6-143622177-T-C
• rs9390123
• ENST00000427704.6:c.13+13855T>C

Variant summary

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

The ENST00000427704.6(PHACTR2):​c.13+13855T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,920 control chromosomes in the GnomAD database, including 27,477 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 0.60 (27477 hom., cov: 31)
• Consequence: PHACTR2 ENST00000427704.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 15 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427704.6. 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_014721.3		c.13+13855T>C		intron	N/A	NP_055536.2	O75167-1
	PHACTR2	NM_001394736.1		c.217+84970T>C		intron	N/A	NP_001381665.1	J3KP75
	PHACTR2	NM_001100166.2		c.13+13855T>C		intron	N/A	NP_001093636.1	O75167-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	ENST00000427704.6	TSL:1	c.13+13855T>C		intron	N/A	ENSP00000391763.2	O75167-1
	PHACTR2	ENST00000367584.8	TSL:5	c.217+84970T>C		intron	N/A	ENSP00000356556.4	J3KP75
	PHACTR2	ENST00000305766.10	TSL:2	c.13+13855T>C		intron	N/A	ENSP00000305530.6	O75167-5

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90898 AN: 151802 Hom.: 27438 Cov.: 31

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.599 AC: 90991 AN: 151920 Hom.: 27477 Cov.: 31 AF XY: 0.597 AC XY: 44301 AN XY: 74236

African (AFR) AF: 0.653 AC: 27028 AN: 41394

American (AMR) AF: 0.525 AC: 8012 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1844 AN: 3468

East Asian (EAS) AF: 0.415 AC: 2144 AN: 5168

South Asian (SAS) AF: 0.433 AC: 2082 AN: 4812

European-Finnish (FIN) AF: 0.612 AC: 6438 AN: 10522

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41432 AN: 67966

Other (OTH) AF: 0.594 AC: 1254 AN: 2112

Alfa AF: 0.602 Hom.: 66441

Bravo AF: 0.597

Asia WGS AF: 0.477 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.24
DANN	Benign	0.32
PhyloP100		-1.9
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: rs9390123; hg19: chr6-143943314;