rs7741628

Positions:

• chr6-143660789-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PHACTR2	NM_001100166.2	c.14-51227C>T		intron_variant
PHACTR2	NM_001394736.1	c.218-51227C>T		intron_variant
PHACTR2	NM_001394738.1	c.14-51227C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR2	ENST00000427704.6	c.14-51227C>T		intron_variant		1
PHACTR2	ENST00000305766.10	c.14-51227C>T		intron_variant		2
PHACTR2	ENST00000367584.8	c.218-51227C>T		intron_variant		5

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

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.402

Alfa AF: 0.427 Hom.: 5987

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7741628; hg19: chr6-143981926; COSMIC: COSV59858226;