2-218228834-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152862.3(ARPC2):​c.206C>T​(p.Ala69Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ARPC2
NM_152862.3 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.60
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31272072).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARPC2NM_152862.3 linkc.206C>T p.Ala69Val missense_variant Exon 4 of 11 ENST00000315717.10 NP_690601.1 O15144Q53R19
ARPC2NM_005731.3 linkc.206C>T p.Ala69Val missense_variant Exon 3 of 10 NP_005722.1 O15144Q53R19
ARPC2XM_017003113.2 linkc.41C>T p.Ala14Val missense_variant Exon 3 of 10 XP_016858602.1
ARPC2XM_047442808.1 linkc.-91C>T 5_prime_UTR_variant Exon 1 of 7 XP_047298764.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARPC2ENST00000315717.10 linkc.206C>T p.Ala69Val missense_variant Exon 4 of 11 1 NM_152862.3 ENSP00000327137.5 O15144

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1443848
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
719242
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 26, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.206C>T (p.A69V) alteration is located in exon 4 (coding exon 3) of the ARPC2 gene. This alteration results from a C to T substitution at nucleotide position 206, causing the alanine (A) at amino acid position 69 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
0.13
BayesDel_addAF
Benign
-0.037
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;T;T
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.95
.;D;D
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.31
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.4
L;.;L
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-1.4
N;N;N
REVEL
Benign
0.10
Sift
Uncertain
0.028
D;D;D
Sift4G
Benign
0.087
T;D;T
Polyphen
0.025
B;.;B
Vest4
0.24
MutPred
0.35
Loss of ubiquitination at K65 (P = 0.0997);Loss of ubiquitination at K65 (P = 0.0997);Loss of ubiquitination at K65 (P = 0.0997);
MVP
0.43
MPC
0.98
ClinPred
0.86
D
GERP RS
5.7
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7
Varity_R
0.27
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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.

Other links and lift over

dbSNP: rs1689567146; hg19: chr2-219093557; API