1-161506414-C-A

Variant names:

• chr1-161506414-C-A
• rs9427397
• NM_001136219.3:c.187C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136219.3(FCGR2A):​c.187C>A​(p.Gln63Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q63R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCGR2A NM_001136219.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 39 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093853444).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136219.3. 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
	FCGR2A	NM_001136219.3	MANE Select	c.187C>A	p.Gln63Lys	missense	Exon 3 of 7	NP_001129691.1	P12318-1
	FCGR2A	NM_021642.5		c.184C>A	p.Gln62Lys	missense	Exon 3 of 7	NP_067674.2	P12318-2
	FCGR2A	NM_001375296.1		c.187C>A	p.Gln63Lys	missense	Exon 3 of 6	NP_001362225.1	A0A8V8TPS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2A	ENST00000271450.12	TSL:1 MANE Select	c.187C>A	p.Gln63Lys	missense	Exon 3 of 7	ENSP00000271450.6	P12318-1
	FCGR2A	ENST00000367972.8	TSL:1	c.184C>A	p.Gln62Lys	missense	Exon 3 of 7	ENSP00000356949.4	P12318-2
	FCGR2A	ENST00000967690.1		c.187C>A	p.Gln63Lys	missense	Exon 3 of 8	ENSP00000637749.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 571

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.0
DANN	Benign	0.47
DEOGEN2	Benign	0.079	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.022	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.50
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.024
Sift	Benign	0.030	D
Sift4G	Benign	0.13	T
Polyphen		0.029	B
Vest4		0.17
MutPred		0.49		Gain of methylation at Q63 (P = 0.0127)
MVP		0.25
MPC		0.28
ClinPred		0.060	T
GERP RS		-2.6
Varity_R		0.54
gMVP		0.46
Mutation Taster		=97/3	polymorphism

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: rs9427397; hg19: chr1-161476204;