rs1082

Positions:

• chr6-143824660-A-C
• chr6-143824660-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100164.2(PHACTR2):​c.*971A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,438 control chromosomes in the GnomAD database, including 8,005 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 0.31 (7993 hom., cov: 32)
  • Exomes 𝑓: 0.28 (12 hom.)
• Consequence: PHACTR2 NM_001100164.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR2	NM_001100164.2	c.*971A>C		3_prime_UTR_variant	13/13	ENST00000440869.7	NP_001093634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR2	ENST00000440869.7	c.*971A>C		3_prime_UTR_variant	13/13	2	NM_001100164.2	ENSP00000417038	A1
PHACTR2	ENST00000367582.7	c.*971A>C		3_prime_UTR_variant	12/12	1		ENSP00000356554	P2
PHACTR2	ENST00000427704.6	c.*971A>C		3_prime_UTR_variant	13/13	1		ENSP00000391763

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47695 AN: 151882 Hom.: 7974 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.283 AC: 124 AN: 438 Hom.: 12 Cov.: 0 AF XY: 0.308 AC XY: 82 AN XY: 266

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.314 AC: 47764 AN: 152000 Hom.: 7993 Cov.: 32 AF XY: 0.315 AC XY: 23395 AN XY: 74314

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.317

Alfa AF: 0.263 Hom.: 5366

Bravo AF: 0.326

Asia WGS AF: 0.407 AC: 1415 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.17
DANN	Benign	0.73

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: rs1082; hg19: chr6-144145797; COSMIC: COSV59852947; COSMIC: COSV59852947;