chr6-143720153-C-G

Variant names:

• chr6-143720153-C-G
• rs9376783
• NM_001100164.2:c.214+7970C>G

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+7970C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,874 control chromosomes in the GnomAD database, including 30,407 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 0.62 (30407 hom., cov: 30)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR2	NM_001100164.2	c.214+7970C>G		intron_variant	Intron 2 of 12	ENST00000440869.7	NP_001093634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR2	ENST00000440869.7	c.214+7970C>G		intron_variant	Intron 2 of 12	2	NM_001100164.2	ENSP00000417038.2

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93475 AN: 151756 Hom.: 30355 Cov.: 30

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.616 AC: 93591 AN: 151874 Hom.: 30407 Cov.: 30 AF XY: 0.609 AC XY: 45194 AN XY: 74198

African (AFR) AF: 0.837 AC: 34697 AN: 41442

American (AMR) AF: 0.497 AC: 7592 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1870 AN: 3466

East Asian (EAS) AF: 0.500 AC: 2573 AN: 5144

South Asian (SAS) AF: 0.579 AC: 2789 AN: 4816

European-Finnish (FIN) AF: 0.478 AC: 5017 AN: 10502

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37039 AN: 67922

Other (OTH) AF: 0.603 AC: 1273 AN: 2112

Alfa AF: 0.592 Hom.: 3433

Bravo AF: 0.624

Asia WGS AF: 0.611 AC: 2122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.71
PhyloP100		-0.11
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: rs9376783; hg19: chr6-144041290;