6-143609267-A-G

Variant names:

• chr6-143609267-A-G
• rs7757372
• ENST00000427704.6:c.13+945A>G

Variant summary

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

The ENST00000427704.6(PHACTR2):​c.13+945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,134 control chromosomes in the GnomAD database, including 9,262 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 0.32 (9262 hom., cov: 33)
• Consequence: PHACTR2 ENST00000427704.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.966
• Publications: 1 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 (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427704.6. 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_014721.3		c.13+945A>G		intron	N/A	NP_055536.2
	PHACTR2	NM_001394736.1		c.217+72060A>G		intron	N/A	NP_001381665.1
	PHACTR2	NM_001100166.2		c.13+945A>G		intron	N/A	NP_001093636.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	ENST00000427704.6	TSL:1	c.13+945A>G		intron	N/A	ENSP00000391763.2
	PHACTR2	ENST00000367584.8	TSL:5	c.217+72060A>G		intron	N/A	ENSP00000356556.4
	PHACTR2	ENST00000305766.10	TSL:2	c.13+945A>G		intron	N/A	ENSP00000305530.6

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48755 AN: 152016 Hom.: 9235 Cov.: 33

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.321 AC: 48836 AN: 152134 Hom.: 9262 Cov.: 33 AF XY: 0.317 AC XY: 23606 AN XY: 74376

African (AFR) AF: 0.539 AC: 22347 AN: 41490

American (AMR) AF: 0.232 AC: 3546 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3468

East Asian (EAS) AF: 0.170 AC: 882 AN: 5192

South Asian (SAS) AF: 0.286 AC: 1382 AN: 4824

European-Finnish (FIN) AF: 0.223 AC: 2356 AN: 10574

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16532 AN: 67984

Other (OTH) AF: 0.316 AC: 666 AN: 2108

Alfa AF: 0.249 Hom.: 2708

Bravo AF: 0.325

Asia WGS AF: 0.268 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.33
PhyloP100		-0.97
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: rs7757372; hg19: chr6-143930404; COSMIC: COSV59851751;