NM_001006658.3:c.2611G>A

Variant names:

• chr1-207475111-G-A
• NM_001006658.3:c.2611G>A

Variant summary

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

The NM_001006658.3(CR2):​c.2611G>A​(p.Val871Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,504 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V871L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CR2 NM_001006658.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.600

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 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
CR2	NM_001006658.3	c.2611G>A	p.Val871Met	missense_variant	Exon 14 of 20	ENST00000367057.8	NP_001006659.1
CR2	NM_001877.5	c.2434G>A	p.Val812Met	missense_variant	Exon 13 of 19		NP_001868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8	c.2611G>A	p.Val871Met	missense_variant	Exon 14 of 20	1	NM_001006658.3	ENSP00000356024.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460504 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726468

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;.;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.045	N
LIST_S2	Uncertain	0.89	D;T;T
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.8	M;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.97	D;D;D
Vest4		0.40
MutPred		0.62		Loss of catalytic residue at V812 (P = 0.0057);.;Loss of catalytic residue at V812 (P = 0.0057);
MVP		0.70
MPC		0.67
ClinPred		0.81	D
GERP RS		0.43
Varity_R		0.12
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-207648456;