rs9427398

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001136219.3(FCGR2A):c.188A>G(p.Gln63Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,613,706 control chromosomes in the GnomAD database, including 11,811 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 935 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10876 hom. )

Consequence

FCGR2A
NM_001136219.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.113

Publications

32 publications found

Variant links:

Genes affected

FCGR2A (HGNC:3616): (Fc gamma receptor IIa) This gene encodes one member of a family of immunoglobulin Fc receptor genes found on the surface of many immune response cells. The protein encoded by this gene is a cell surface receptor found on phagocytic cells such as macrophages and neutrophils, and is involved in the process of phagocytosis and clearing of immune complexes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2008]

FCGR2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.004311353).

BP6

Variant 1-161506415-A-G is Benign according to our data. Variant chr1-161506415-A-G is described in ClinVar as Benign. ClinVar VariationId is 402850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR2A	NM_001136219.3 link	c.188A>G	p.Gln63Arg	missense_variant	Exon 3 of 7	ENST00000271450.12	NP_001129691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR2A	ENST00000271450.12 link	c.188A>G	p.Gln63Arg	missense_variant	Exon 3 of 7	1	NM_001136219.3	ENSP00000271450.6

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15396

AN:

152072

Hom.:

933

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.0779

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0859

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.115

GnomAD2 exomes

AF:

0.108

AC:

27138

AN:

251424

AF XY:

0.112

show subpopulations

Gnomad AFR exome

AF:

0.0626

Gnomad AMR exome

AF:

0.0686

Gnomad ASJ exome

AF:

0.269

Gnomad EAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.131

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.116

AC:

169729

AN:

1461518

Hom.:

10876

Cov.:

AF XY:

0.117

AC XY:

84876

AN XY:

727068

show subpopulations

African (AFR)

AF:

0.0608

AC:

2035

AN:

33448

American (AMR)

AF:

0.0717

AC:

3207

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

7113

AN:

26124

East Asian (EAS)

AF:

0.000227

AC:

AN:

39630

South Asian (SAS)

AF:

0.0921

AC:

7946

AN:

86256

European-Finnish (FIN)

AF:

0.116

AC:

6195

AN:

53414

Middle Eastern (MID)

AF:

0.201

AC:

1158

AN:

5764

European-Non Finnish (NFE)

AF:

0.121

AC:

134910

AN:

1111808

Other (OTH)

AF:

0.119

AC:

7156

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

10779

21558

32338

43117

53896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4728

9456

14184

18912

23640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.101

AC:

15401

AN:

152188

Hom.:

935

Cov.:

AF XY:

0.101

AC XY:

7536

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0628

AC:

2610

AN:

41540

American (AMR)

AF:

0.104

AC:

1591

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

911

AN:

3470

East Asian (EAS)

AF:

0.000774

AC:

AN:

5170

South Asian (SAS)

AF:

0.0858

AC:

413

AN:

4814

European-Finnish (FIN)

AF:

0.111

AC:

1175

AN:

10614

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8342

AN:

67978

Other (OTH)

AF:

0.114

AC:

241

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

714

1427

2141

2854

3568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0886

Hom.:

1446

Bravo

AF:

0.102

TwinsUK

AF:

0.124

AC:

460

ALSPAC

AF:

0.122

AC:

471

ESP6500AA

AF:

0.0663

AC:

292

ESP6500EA

AF:

0.132

AC:

1133

ExAC

AF:

0.108

AC:

13063

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

EpiCase

AF:

0.143

EpiControl

AF:

0.148

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

FCGR2A-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.8

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.0

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.24

T;T

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

.;M

PhyloP100

0.11

PrimateAI

Benign

0.17

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.034

Sift

Benign

0.22

T;T

Sift4G

Benign

0.24

T;T

Vest4

0.024

ClinPred

0.0065

GERP RS

1.3

Varity_R

0.33

gMVP

0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over