Variant 2-218217477-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.58

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 Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 978 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPC2	NM_152862.3 linkuse as main transcript	c.7C>T	p.Leu3Leu	synonymous_variant	2/11	ENST00000315717.10	NP_690601.1	O15144Q53R19
ARPC2	NM_005731.3 linkuse as main transcript	c.7C>T	p.Leu3Leu	synonymous_variant	1/10		NP_005722.1	O15144Q53R19
ARPC2	XM_017003113.2 linkuse as main transcript	c.-92+223C>T		intron_variant			XP_016858602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPC2	ENST00000315717.10 linkuse as main transcript	c.7C>T	p.Leu3Leu	synonymous_variant	2/11	1	NM_152862.3	ENSP00000327137.5		O15144

Frequencies

GnomAD3 genomes

AF:

0.00634

AC:

965

AN:

152190

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00986

AC:

2465

AN:

250090

Hom.:

AF XY:

0.00854

AC XY:

1158

AN XY:

135596

show subpopulations

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 SAS exome

AF:

0.00111

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.:

Cov.:

AF XY:

0.00618

AC XY:

4494

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.0372

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.0222

Gnomad4 SAS exome

AF:

0.00115

Gnomad4 FIN exome

AF:

0.00382

Gnomad4 NFE exome

AF:

0.00549

Gnomad4 OTH exome

AF:

0.00591

GnomAD4 genome

AF:

0.00642

AC:

978

AN:

152308

Hom.:

Cov.:

AF XY:

0.00630

AC XY:

469

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0147

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.00504

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00489

Hom.:

Bravo

AF:

0.00901

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.00507

EpiControl

AF:

0.00557

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 13, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.97

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