rs778193518

Variant names:

• chr6-143760592-C-A
• rs778193518
• NM_001100164.2:c.646C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-143760592-C-A
• chr6-143760592-C-G
• chr6-143760592-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001100164.2(PHACTR2):​c.646C>A​(p.Pro216Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: PHACTR2 NM_001100164.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100164.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	NM_001100164.2	MANE Select	c.646C>A	p.Pro216Thr	missense	Exon 5 of 13	NP_001093634.1	O75167-4
	PHACTR2	NM_014721.3		c.613C>A	p.Pro205Thr	missense	Exon 5 of 13	NP_055536.2	O75167-1
	PHACTR2	NM_001394736.1		c.626-4669C>A		intron	N/A	NP_001381665.1	J3KP75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	ENST00000440869.7	TSL:2 MANE Select	c.646C>A	p.Pro216Thr	missense	Exon 5 of 13	ENSP00000417038.2	O75167-4
	PHACTR2	ENST00000427704.6	TSL:1	c.613C>A	p.Pro205Thr	missense	Exon 5 of 13	ENSP00000391763.2	O75167-1
	PHACTR2	ENST00000367582.7	TSL:1	c.455-4669C>A		intron	N/A	ENSP00000356554.3	O75167-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248802 AF XY: 0.0000148

Gnomad AFR exome AF: 0.0000648

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461702 Hom.: 0 Cov.: 33 AF XY: 0.0000248 AC XY: 18 AN XY: 727132

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111868

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.3
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.12
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.017	D
Polyphen		0.99	D
Vest4		0.56
MutPred		0.23		Gain of phosphorylation at P205 (P = 0.0174)
MVP		0.69
MPC		0.41
ClinPred		0.93	D
GERP RS		6.1
Varity_R		0.20
gMVP		0.24
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs778193518; hg19: chr6-144081729; COSMIC: COSV59857700;