rs1265956994

Variant names:

• chr6-143712031-A-G
• NM_001100164.2:c.62A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-143712031-A-G
• chr6-143712031-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001100164.2(PHACTR2):​c.62A>G​(p.Lys21Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,439,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PHACTR2 NM_001100164.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.37

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1271283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR2	NM_001100164.2	c.62A>G	p.Lys21Arg	missense_variant	Exon 2 of 13	ENST00000440869.7	NP_001093634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR2	ENST00000440869.7	c.62A>G	p.Lys21Arg	missense_variant	Exon 2 of 13	2	NM_001100164.2	ENSP00000417038.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1439214 Hom.: 0 Cov.: 30 AF XY: 0.00000280 AC XY: 2 AN XY: 715026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0069	.;T;.;.;.;T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.0097
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	D;T;D;T;D;D;D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.13	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N;N;.;.;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.75	N;N;N;N;N;N;N
REVEL	Benign	0.039
Sift	Benign	0.27	T;T;T;T;T;T;T
Sift4G	Benign	0.35	T;D;T;T;T;T;T
Polyphen		0.015, 0.026, 0.011	.;B;B;B;B;.;.
Vest4		0.18
MutPred		0.14		.;Loss of ubiquitination at K10 (P = 8e-04);Loss of ubiquitination at K10 (P = 8e-04);.;.;.;.;
MVP		0.51
MPC		0.058
ClinPred		0.89	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.17
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-144033168;