rs6931865

Variant names:

• chr6-143758717-A-G
• rs6931865
• NM_001100164.2:c.455-1684A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-143758717-A-G
• chr6-143758717-A-T

Variant summary

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

The NM_001100164.2(PHACTR2):​c.455-1684A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,054 control chromosomes in the GnomAD database, including 34,312 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 0.67 (34312 hom., cov: 32)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100164.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	NM_001100164.2	MANE Select	c.455-1684A>G		intron	N/A	NP_001093634.1
	PHACTR2	NM_014721.3		c.422-1684A>G		intron	N/A	NP_055536.2
	PHACTR2	NM_001394736.1		c.625+4805A>G		intron	N/A	NP_001381665.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	ENST00000440869.7	TSL:2 MANE Select	c.455-1684A>G		intron	N/A	ENSP00000417038.2
	PHACTR2	ENST00000427704.6	TSL:1	c.422-1684A>G		intron	N/A	ENSP00000391763.2
	PHACTR2	ENST00000367582.7	TSL:1	c.454+4805A>G		intron	N/A	ENSP00000356554.3

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101881 AN: 151934 Hom.: 34261 Cov.: 32

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.671 AC: 101994 AN: 152054 Hom.: 34312 Cov.: 32 AF XY: 0.670 AC XY: 49830 AN XY: 74336

African (AFR) AF: 0.710 AC: 29438 AN: 41484

American (AMR) AF: 0.650 AC: 9928 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2164 AN: 3470

East Asian (EAS) AF: 0.644 AC: 3323 AN: 5160

South Asian (SAS) AF: 0.718 AC: 3460 AN: 4816

European-Finnish (FIN) AF: 0.628 AC: 6637 AN: 10562

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44882 AN: 67966

Other (OTH) AF: 0.660 AC: 1393 AN: 2112

Alfa AF: 0.662 Hom.: 148977

Bravo AF: 0.674

Asia WGS AF: 0.695 AC: 2415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.72
PhyloP100		0.20
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: rs6931865; hg19: chr6-144079854; COSMIC: COSV107371762; COSMIC: COSV107371762;