rs10979

Variant names:

• chr6-143568902-G-A
• rs10979
• ENST00000789359.1:n.446C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000789359.1(ENSG00000302762):​n.446C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,796 control chromosomes in the GnomAD database, including 28,771 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 0.61 (28771 hom., cov: 32)
• Consequence: ENSG00000302762 ENST00000789359.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 8 publications found

Genes affected

ENSG00000302762 (HGNC:):

PHACTR2-AS1 (HGNC:40943): (PHACTR2 antisense RNA 1)

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]

PHACTR2 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR2-AS1	NR_027113.2	n.438C>T		non_coding_transcript_exon_variant	Exon 1 of 3
PHACTR2	NM_001394736.1	c.217+31695G>A		intron_variant	Intron 1 of 11		NP_001381665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000302762	ENST00000789359.1	n.446C>T		non_coding_transcript_exon_variant	Exon 1 of 1
PHACTR2	ENST00000367584.8	c.217+31695G>A		intron_variant	Intron 1 of 11	5		ENSP00000356556.4

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92863 AN: 151680 Hom.: 28746 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.612 AC: 92936 AN: 151796 Hom.: 28771 Cov.: 32 AF XY: 0.612 AC XY: 45357 AN XY: 74170

African (AFR) AF: 0.590 AC: 24440 AN: 41396

American (AMR) AF: 0.528 AC: 8052 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2122 AN: 3468

East Asian (EAS) AF: 0.386 AC: 1987 AN: 5152

South Asian (SAS) AF: 0.549 AC: 2640 AN: 4812

European-Finnish (FIN) AF: 0.648 AC: 6806 AN: 10510

Middle Eastern (MID) AF: 0.716 AC: 209 AN: 292

European-Non Finnish (NFE) AF: 0.662 AC: 44918 AN: 67884

Other (OTH) AF: 0.604 AC: 1275 AN: 2110

Alfa AF: 0.642 Hom.: 134687

Bravo AF: 0.599

Asia WGS AF: 0.537 AC: 1867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.28
DANN	Benign	0.59
PhyloP100		-0.077
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10979; hg19: chr6-143890039;