dbSNP rs1082: PHACTR2:c.*971A>C (chr6-143824660-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001100164.2(PHACTR2):c.*971A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,438 control chromosomes in the GnomAD database, including 8,005 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 0.31 ( 7993 hom., cov: 32)

Exomes 𝑓: 0.28 ( 12 hom. )

Consequence

PHACTR2
NM_001100164.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0410

Publications

17 publications found

Variant links:

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]

PHACTR2 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

PHACTR2 links:

ENSG00000257065 (HGNC:):

ENSG00000257065 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR2	NM_001100164.2 link	c.*971A>C		3_prime_UTR_variant	Exon 13 of 13	ENST00000440869.7	NP_001093634.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PHACTR2	ENST00000440869.7 link	c.*971A>C	3_prime_UTR_variant	Exon 13 of 13	2	NM_001100164.2	ENSP00000417038.2
PHACTR2	ENST00000427704.6 link	c.*971A>C	3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000391763.2
PHACTR2	ENST00000367582.7 link	c.*971A>C	3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000356554.3
ENSG00000257065	ENST00000545614.1 link	n.*234+737A>C	intron_variant	Intron 2 of 4	5		ENSP00000456586.1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47695

AN:

151882

Hom.:

7974

Cov.:

show subpopulations

Gnomad AFR

AF:

0.415

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.447

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.241

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.311

GnomAD4 exome

AF:

0.283

AC:

124

AN:

438

Hom.:

Cov.:

AF XY:

0.308

AC XY:

AN XY:

266

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.285

AC:

122

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.314

AC:

47764

AN:

152000

Hom.:

7993

Cov.:

AF XY:

0.315

AC XY:

23395

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.415

AC:

17178

AN:

41422

American (AMR)

AF:

0.329

AC:

5031

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1123

AN:

3472

East Asian (EAS)

AF:

0.446

AC:

2311

AN:

5176

South Asian (SAS)

AF:

0.367

AC:

1762

AN:

4804

European-Finnish (FIN)

AF:

0.241

AC:

2551

AN:

10580

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.248

AC:

16841

AN:

67938

Other (OTH)

AF:

0.317

AC:

669

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1610

3220

4830

6440

8050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.276

Hom.:

8746

Bravo

AF:

0.326

Asia WGS

AF:

0.407

AC:

1415

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.17

(source)

DANN

Benign

0.73

PhyloP100

-0.041

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over