19-47341101-C-A

Variant names:

• chr19-47341101-C-A
• rs541823800
• NM_001271749.2:c.302C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001271749.2(C5AR2):​c.302C>A​(p.Pro101Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: C5AR2 NM_001271749.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.604

Genes affected

C5AR2 (HGNC:4527): (complement C5a receptor 2) This gene encodes a G-protein coupled receptor 1 family member involved in the complement system of the innate immune response. Unlike classical G-protein coupled receptors, the encoded protein does not associate with intracellular G-proteins. It may instead modulate signal transduction through the beta-arrestin pathway, and may alternatively act as a decoy receptor. This gene may be involved in coronary artery disease and in the pathogenesis of sepsis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5AR2	NM_001271749.2	c.302C>A	p.Pro101Gln	missense_variant	Exon 2 of 2	ENST00000595464.3	NP_001258678.1
C5AR2	NM_001271750.2	c.302C>A	p.Pro101Gln	missense_variant	Exon 2 of 2		NP_001258679.1
C5AR2	NM_018485.3	c.302C>A	p.Pro101Gln	missense_variant	Exon 2 of 2		NP_060955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5AR2	ENST00000595464.3	c.302C>A	p.Pro101Gln	missense_variant	Exon 2 of 2	1	NM_001271749.2	ENSP00000472620.1
C5AR2	ENST00000600626.1	c.302C>A	p.Pro101Gln	missense_variant	Exon 2 of 2	1		ENSP00000471184.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152232 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152350 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74500

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.302C>A (p.P101Q) alteration is located in exon 2 (coding exon 1) of the C5AR2 gene. This alteration results from a C to A substitution at nucleotide position 302, causing the proline (P) at amino acid position 101 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;T
Eigen	Benign	0.099
Eigen_PC	Benign	-0.067
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.54	.;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Benign	0.32	T
Sift4G	Benign	0.10	T;T
Polyphen		0.98	D;D
Vest4		0.38
MutPred		0.73		Loss of methylation at R96 (P = 0.1262);Loss of methylation at R96 (P = 0.1262);
MVP		0.66
MPC		0.71
ClinPred		0.98	D
GERP RS		3.2
Varity_R		0.23
gMVP		0.10

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

Other links and lift over

dbSNP: rs541823800; hg19: chr19-47844358;