rs1015340

chr6-143714220-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+2037C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,034 control chromosomes in the GnomAD database, including 18,333 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 0.49 (18333 hom., cov: 32)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR2	NM_001100164.2	c.214+2037C>T		intron_variant		ENST00000440869.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR2	ENST00000440869.7	c.214+2037C>T		intron_variant		2	NM_001100164.2	A1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74066 AN: 151916 Hom.: 18309 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.488 AC: 74141 AN: 152034 Hom.: 18333 Cov.: 32 AF XY: 0.485 AC XY: 36045 AN XY: 74310

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.499

Alfa AF: 0.511 Hom.: 33572

Bravo AF: 0.479

Asia WGS AF: 0.548 AC: 1904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.38
Dann	Benign	0.44

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: rs1015340; hg19: chr6-144035357;