6-143713902-C-G

Variant names:

• chr6-143713902-C-G
• rs1040638
• NM_001100164.2:c.214+1719C>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+1719C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,896 control chromosomes in the GnomAD database, including 17,701 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 (17701 hom., cov: 32)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR2	NM_001100164.2	c.214+1719C>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+1719C>G		intron_variant	Intron 2 of 12	2	NM_001100164.2	ENSP00000417038.2

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72778 AN: 151778 Hom.: 17676 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.480 AC: 72860 AN: 151896 Hom.: 17701 Cov.: 32 AF XY: 0.477 AC XY: 35440 AN XY: 74232

African (AFR) AF: 0.431 AC: 17852 AN: 41400

American (AMR) AF: 0.442 AC: 6755 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1772 AN: 3468

East Asian (EAS) AF: 0.431 AC: 2225 AN: 5168

South Asian (SAS) AF: 0.539 AC: 2595 AN: 4814

European-Finnish (FIN) AF: 0.461 AC: 4851 AN: 10524

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35077 AN: 67922

Other (OTH) AF: 0.492 AC: 1041 AN: 2114

Alfa AF: 0.357 Hom.: 964

Bravo AF: 0.470

Asia WGS AF: 0.539 AC: 1870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.49
PhyloP100		0.093
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1040638; hg19: chr6-144035039;