chr2-218249361-C-T

Variant names:

• chr2-218249361-C-T
• rs74349827
• NM_152862.3:c.677-3C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_152862.3(ARPC2):​c.677-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,609,068 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (41 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (35 hom.)
• Consequence: ARPC2 NM_152862.3 splice_region, intron
• Scores: Splicing: ADA: 0.001327
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.77
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 2-218249361-C-T is Benign according to our data. Variant chr2-218249361-C-T is described in ClinVar as Benign. ClinVar VariationId is 791124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0123 (1869/152264) while in subpopulation AFR AF = 0.0423 (1758/41520). AF 95% confidence interval is 0.0407. There are 41 homozygotes in GnomAd4. There are 907 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1869 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152862.3. 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
	ARPC2	NM_152862.3	MANE Select	c.677-3C>T		splice_region intron	N/A	NP_690601.1	O15144
	ARPC2	NM_005731.3		c.677-3C>T		splice_region intron	N/A	NP_005722.1	Q53R19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPC2	ENST00000315717.10	TSL:1 MANE Select	c.677-3C>T		splice_region intron	N/A	ENSP00000327137.5	O15144
	ARPC2	ENST00000295685.14	TSL:1	c.677-3C>T		splice_region intron	N/A	ENSP00000295685.10	O15144
	ARPC2	ENST00000943698.1		c.701-3C>T		splice_region intron	N/A	ENSP00000613757.1

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1868 AN: 152146 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00353 AC: 879 AN: 248896 AF XY: 0.00265

Gnomad AFR exome AF: 0.0436

Gnomad AMR exome AF: 0.00219

Gnomad ASJ exome AF: 0.00770

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00137 AC: 1993 AN: 1456804 Hom.: 35 Cov.: 30 AF XY: 0.00121 AC XY: 879 AN XY: 725034

African (AFR) AF: 0.0419 AC: 1395 AN: 33284

American (AMR) AF: 0.00245 AC: 108 AN: 44112

Ashkenazi Jewish (ASJ) AF: 0.00833 AC: 217 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5756

European-Non Finnish (NFE) AF: 0.0000523 AC: 58 AN: 1108550

Other (OTH) AF: 0.00331 AC: 199 AN: 60198

GnomAD4 genome AF: 0.0123 AC: 1869 AN: 152264 Hom.: 41 Cov.: 32 AF XY: 0.0122 AC XY: 907 AN XY: 74446

African (AFR) AF: 0.0423 AC: 1758 AN: 41520

American (AMR) AF: 0.00366 AC: 56 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00779 AC: 27 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68036

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00646 Hom.: 10

Bravo AF: 0.0133

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000416

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0013
dbscSNV1_RF	Benign	0.052
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

Other links and lift over

dbSNP: rs74349827; hg19: chr2-219114084;