Variant 1-161509873-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001136219.3(FCGR2A):c.418A>G(p.Met140Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000841 in 1,614,220 control chromosomes in the GnomAD database, including 1 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 Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 1 hom. )

Consequence

FCGR2A
NM_001136219.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: -2.47

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0073492527).

BP6

Variant 1-161509873-A-G is Benign according to our data. Variant chr1-161509873-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1285036.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-161509873-A-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR2A	NM_001136219.3 link	c.418A>G	p.Met140Val	missense_variant	4/7	ENST00000271450.12	NP_001129691.1	P12318-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR2A	ENST00000271450.12 link	c.418A>G	p.Met140Val	missense_variant	4/7	1	NM_001136219.3	ENSP00000271450.6		P12318-1

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

203

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000823

AC:

207

AN:

251482

Hom.:

AF XY:

0.000736

AC XY:

100

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00301

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.000607

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.000789

AC:

1153

AN:

1461874

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

556

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00314

Gnomad4 AMR exome

AF:

0.00125

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.000711

Gnomad4 NFE exome

AF:

0.000725

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152346

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00325

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000721

Hom.:

Bravo

AF:

0.00146

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000865

AC:

105

EpiCase

AF:

0.00125

EpiControl

AF:

0.000948

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	FCGR2A: BS1 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.0010

DANN

Benign

0.27

DEOGEN2

Benign

0.023

.;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.036

T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.0073

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.1

.;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.090

N;N

REVEL

Benign

0.019

Sift

Benign

0.43

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.058

MVP

0.21

MPC

0.22

ClinPred

0.0013

GERP RS

-5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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