rs1040638

Positions:

• chr6-143713902-C-G
• chr6-143713902-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR2	NM_001100164.2	c.214+1719C>G		intron_variant		ENST00000440869.7	NP_001093634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR2	ENST00000440869.7	c.214+1719C>G		intron_variant		2	NM_001100164.2	ENSP00000417038	A1

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

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.492

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1040638; hg19: chr6-144035039;