chr6-143714327-T-C

Position:

• chr6-143714327-T-C

Variant summary

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

The NM_001100164.2(PHACTR2):​c.214+2144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,114 control chromosomes in the GnomAD database, including 17,555 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 (17555 hom., cov: 33)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR2	NM_001100164.2	c.214+2144T>C		intron_variant		ENST00000440869.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR2	ENST00000440869.7	c.214+2144T>C		intron_variant		2	NM_001100164.2	A1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72292 AN: 151996 Hom.: 17538 Cov.: 33

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.476 AC: 72358 AN: 152114 Hom.: 17555 Cov.: 33 AF XY: 0.474 AC XY: 35212 AN XY: 74360

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.496

Alfa AF: 0.511 Hom.: 27244

Bravo AF: 0.466

Asia WGS AF: 0.552 AC: 1915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.60

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: rs1015341; hg19: chr6-144035464;