rs3748076

chr6-143757963-G-Achr6-143757963-G-C

Variant summary

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

The NM_001100164.2(PHACTR2):c.455-2438G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 131,398 control chromosomes in the GnomAD database, including 18,517 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 0.56 (18517 hom., cov: 26)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR2	NM_001100164.2	c.455-2438G>A		intron_variant		ENST00000440869.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR2	ENST00000440869.7	c.455-2438G>A		intron_variant		2	NM_001100164.2	A1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 74135 AN: 131322 Hom.: 18491 Cov.: 26

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.565 AC: 74202 AN: 131398 Hom.: 18517 Cov.: 26 AF XY: 0.567 AC XY: 36498 AN XY: 64412

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.558

Alfa AF: 0.459 Hom.: 1061

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.3
Dann	Benign	0.63

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: rs3748076; hg19: chr6-144079100;