Variant 2-218238738-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152862.3(ARPC2):c.343A>G(p.Met115Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ARPC2
NM_152862.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.76

Variant links:

Genes affected

ARPC2 (HGNC:705): (actin related protein 2/3 complex subunit 2) This gene encodes one of seven subunits of the human Arp2/3 protein complex. The Arp2/3 protein complex has been implicated in the control of actin polymerization in cells and has been conserved through evolution. The exact role of the protein encoded by this gene, the p34 subunit, has yet to be determined. Two alternatively spliced variants have been characterized to date. Additional alternatively spliced variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

ARPC2 links:

ARPC2 (HGNC:):

ARPC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPC2	NM_152862.3 linkuse as main transcript	c.343A>G	p.Met115Val	missense_variant	6/11	ENST00000315717.10	NP_690601.1	O15144Q53R19
ARPC2	XM_047442808.1 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	2/7		XP_047298764.1
ARPC2	NM_005731.3 linkuse as main transcript	c.343A>G	p.Met115Val	missense_variant	5/10		NP_005722.1	O15144Q53R19
ARPC2	XM_017003113.2 linkuse as main transcript	c.178A>G	p.Met60Val	missense_variant	5/10		XP_016858602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPC2	ENST00000315717.10 linkuse as main transcript	c.343A>G	p.Met115Val	missense_variant	6/11	1	NM_152862.3	ENSP00000327137.5		O15144

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251464

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727210

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 05, 2024

The c.343A>G (p.M115V) alteration is located in exon 6 (coding exon 5) of the ARPC2 gene. This alteration results from a A to G substitution at nucleotide position 343, causing the methionine (M) at amino acid position 115 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

0.025

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.0039

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.5

L;L

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.21

Sift

Benign

0.068

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.0

B;B

Vest4

0.70

MutPred

0.67

Gain of catalytic residue at M115 (P = 0.0424);Gain of catalytic residue at M115 (P = 0.0424);

MVP

0.74

MPC

1.0

ClinPred

0.34

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over