rs7741628

Variant names:

• chr6-143660789-C-T
• rs7741628
• ENST00000427704.6:c.14-51227C>T

Variant summary

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

The ENST00000427704.6(PHACTR2):​c.14-51227C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,864 control chromosomes in the GnomAD database, including 11,549 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 0.38 (11549 hom., cov: 32)
• Consequence: PHACTR2 ENST00000427704.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR2	NM_014721.3	c.14-51227C>T		intron_variant	Intron 1 of 12		NP_055536.2
PHACTR2	NM_001394736.1	c.218-51227C>T		intron_variant	Intron 1 of 11		NP_001381665.1
PHACTR2	NM_001100166.2	c.14-51227C>T		intron_variant	Intron 1 of 11		NP_001093636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR2	ENST00000427704.6	c.14-51227C>T		intron_variant	Intron 1 of 12	1		ENSP00000391763.2
PHACTR2	ENST00000367584.8	c.218-51227C>T		intron_variant	Intron 1 of 11	5		ENSP00000356556.4
PHACTR2	ENST00000305766.10	c.14-51227C>T		intron_variant	Intron 1 of 11	2		ENSP00000305530.6

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57594 AN: 151746 Hom.: 11535 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.379 AC: 57620 AN: 151864 Hom.: 11549 Cov.: 32 AF XY: 0.382 AC XY: 28348 AN XY: 74168

African (AFR) AF: 0.232 AC: 9615 AN: 41444

American (AMR) AF: 0.371 AC: 5663 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1379 AN: 3466

East Asian (EAS) AF: 0.440 AC: 2276 AN: 5172

South Asian (SAS) AF: 0.521 AC: 2508 AN: 4812

European-Finnish (FIN) AF: 0.434 AC: 4550 AN: 10492

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.444 AC: 30162 AN: 67900

Other (OTH) AF: 0.402 AC: 849 AN: 2114

Alfa AF: 0.425 Hom.: 6717

Bravo AF: 0.359

Asia WGS AF: 0.506 AC: 1758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.2
DANN	Benign	0.78
PhyloP100		0.29
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: rs7741628; hg19: chr6-143981926; COSMIC: COSV59858226;