rs7757372

Positions:

• chr6-143609267-A-G
• chr6-143609267-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR2	NM_001100166.2	c.13+945A>G		intron_variant			NP_001093636.1
PHACTR2	NM_001394736.1	c.217+72060A>G		intron_variant			NP_001381665.1
PHACTR2	NM_001394738.1	c.13+945A>G		intron_variant			NP_001381667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR2	ENST00000427704.6	c.13+945A>G		intron_variant		1		ENSP00000391763
PHACTR2	ENST00000305766.10	c.13+945A>G		intron_variant		2		ENSP00000305530
PHACTR2	ENST00000367584.8	c.217+72060A>G		intron_variant		5		ENSP00000356556

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

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.316

Alfa AF: 0.246 Hom.: 2357

Bravo AF: 0.325

Asia WGS AF: 0.268 AC: 935 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	0.22
DANN	Benign	0.33

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: rs7757372; hg19: chr6-143930404; COSMIC: COSV59851751;