chr2-218217477-C-T

Variant names:

• chr2-218217477-C-T
• rs144937426
• NM_152862.3:c.7C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_152862.3(ARPC2):​c.7C>T​(p.Leu3Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00642 in 1,613,918 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (11 hom., cov: 33)
  • Exomes 𝑓: 0.0064 (74 hom.)
• Consequence: ARPC2 NM_152862.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.58
• Publications: 6 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]

ENSG00000305602 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 2-218217477-C-T is Benign according to our data. Variant chr2-218217477-C-T is described in ClinVar as Benign. ClinVar VariationId is 781689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.58 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00642 (978/152308) while in subpopulation AMR AF = 0.0265 (406/15300). AF 95% confidence interval is 0.0244. There are 11 homozygotes in GnomAd4. There are 469 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 978 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.7C>T	p.Leu3Leu	synonymous	Exon 2 of 11	NP_690601.1	O15144
	ARPC2	NM_005731.3		c.7C>T	p.Leu3Leu	synonymous	Exon 1 of 10	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.7C>T	p.Leu3Leu	synonymous	Exon 2 of 11	ENSP00000327137.5	O15144
	ARPC2	ENST00000295685.14	TSL:1	c.7C>T	p.Leu3Leu	synonymous	Exon 1 of 10	ENSP00000295685.10	O15144
	ARPC2	ENST00000943698.1		c.7C>T	p.Leu3Leu	synonymous	Exon 2 of 12	ENSP00000613757.1

Frequencies

GnomAD3 genomes AF: 0.00634 AC: 965 AN: 152190 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0149

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00504

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00986 AC: 2465 AN: 250090 AF XY: 0.00854

Gnomad AFR exome AF: 0.00193

Gnomad AMR exome AF: 0.0374

Gnomad ASJ exome AF: 0.00110

Gnomad EAS exome AF: 0.0211

Gnomad FIN exome AF: 0.00375

Gnomad NFE exome AF: 0.00523

Gnomad OTH exome AF: 0.00640

GnomAD4 exome AF: 0.00641 AC: 9376 AN: 1461610 Hom.: 74 Cov.: 33 AF XY: 0.00618 AC XY: 4494 AN XY: 727116

African (AFR) AF: 0.00134 AC: 45 AN: 33472

American (AMR) AF: 0.0372 AC: 1664 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.000574 AC: 15 AN: 26122

East Asian (EAS) AF: 0.0222 AC: 880 AN: 39692

South Asian (SAS) AF: 0.00115 AC: 99 AN: 86252

European-Finnish (FIN) AF: 0.00382 AC: 204 AN: 53398

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.00549 AC: 6103 AN: 1111818

Other (OTH) AF: 0.00591 AC: 357 AN: 60376

GnomAD4 genome AF: 0.00642 AC: 978 AN: 152308 Hom.: 11 Cov.: 33 AF XY: 0.00630 AC XY: 469 AN XY: 74468

African (AFR) AF: 0.00195 AC: 81 AN: 41584

American (AMR) AF: 0.0265 AC: 406 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.0147 AC: 76 AN: 5158

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00504 AC: 343 AN: 68036

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00572 Hom.: 6

Bravo AF: 0.00901

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.00507

EpiControl AF: 0.00557

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	-0.25
CADD	Benign	15
DANN	Benign	0.97
PhyloP100		2.6
PromoterAI		0.070	Neutral
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs144937426; hg19: chr2-219082200;