2-218228834-C-T

Variant names:

• chr2-218228834-C-T
• rs1689567146
• NM_152862.3:c.206C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.60

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]

ACMG classification

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
ARPC2	NM_152862.3	c.206C>T	p.Ala69Val	missense_variant	Exon 4 of 11	ENST00000315717.10	NP_690601.1
ARPC2	NM_005731.3	c.206C>T	p.Ala69Val	missense_variant	Exon 3 of 10		NP_005722.1
ARPC2	XM_017003113.2	c.41C>T	p.Ala14Val	missense_variant	Exon 3 of 10		XP_016858602.1
ARPC2	XM_047442808.1	c.-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
ARPC2	ENST00000315717.10	c.206C>T	p.Ala69Val	missense_variant	Exon 4 of 11	1	NM_152862.3	ENSP00000327137.5

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

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

Other links and lift over

dbSNP: rs1689567146; hg19: chr2-219093557;