1-207474298-G-T

Variant names:

• chr1-207474298-G-T
• rs151093663
• NM_001006658.3:c.2298G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001006658.3(CR2):​c.2298G>T​(p.Trp766Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. W766L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CR2 NM_001006658.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.19

Genes affected

CR2 (HGNC:2336): (complement C3d receptor 2) This gene encodes a membrane protein, which functions as a receptor for Epstein-Barr virus (EBV) binding on B and T lymphocytes. Genetic variations in this gene are associated with susceptibility to systemic lupus erythematosus type 9 (SLEB9). Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR2	NM_001006658.3	c.2298G>T	p.Trp766Cys	missense_variant	Exon 13 of 20	ENST00000367057.8	NP_001006659.1
CR2	NM_001877.5	c.2121G>T	p.Trp707Cys	missense_variant	Exon 12 of 19		NP_001868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8	c.2298G>T	p.Trp766Cys	missense_variant	Exon 13 of 20	1	NM_001006658.3	ENSP00000356024.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.88	D;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Pathogenic	4.3	H;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-10	D;D;D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.78
MutPred		0.50		Loss of ubiquitination at K710 (P = 0.0596);.;Loss of ubiquitination at K710 (P = 0.0596);
MVP		0.95
MPC		0.87
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.74
gMVP		0.99

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: rs151093663; hg19: chr1-207647643;