rs34349246

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000640301.1(CR2):c.67C>T(p.Arg23Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,613,944 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R23L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.021 ( 45 hom., cov: 32)

Exomes 𝑓: 0.014 ( 208 hom. )

Consequence

CR2
ENST00000640301.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.97

Publications

10 publications found

Variant links:

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]

CR2 Gene-Disease associations (from GenCC):

immunodeficiency, common variable, 7
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
common variable immunodeficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

CR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019263625).

BP6

Variant 1-207472818-C-T is Benign according to our data. Variant chr1-207472818-C-T is described in ClinVar as Benign. ClinVar VariationId is 473095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0209 (3189/152252) while in subpopulation AFR AF = 0.032 (1329/41534). AF 95% confidence interval is 0.0306. There are 45 homozygotes in GnomAd4. There are 1512 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 45 Unknown,AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000640301.1. 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
	CR2	NM_001006658.3	MANE Select	c.1617C>T	p.Thr539Thr	synonymous	Exon 10 of 20	NP_001006659.1	P20023-3
	CR2	NM_001877.5		c.1617C>T	p.Thr539Thr	synonymous	Exon 10 of 19	NP_001868.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CR2	ENST00000640301.1	TSL:1	c.67C>T	p.Arg23Trp	missense	Exon 2 of 2	ENSP00000491608.1	A0A1W2PPV2
CR2	ENST00000367057.8	TSL:1 MANE Select	c.1617C>T	p.Thr539Thr	synonymous	Exon 10 of 20	ENSP00000356024.3	P20023-3
CR2	ENST00000367058.7	TSL:1	c.1617C>T	p.Thr539Thr	synonymous	Exon 10 of 19	ENSP00000356025.3	P20023-1

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

3190

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0321

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0162

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.0363

GnomAD2 exomes

AF:

0.0151

AC:

3806

AN:

251298

AF XY:

0.0150

show subpopulations

Gnomad AFR exome

AF:

0.0340

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.0211

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0157

Gnomad NFE exome

AF:

0.0169

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0143

AC:

20902

AN:

1461692

Hom.:

208

Cov.:

AF XY:

0.0142

AC XY:

10350

AN XY:

727146

show subpopulations

African (AFR)

AF:

0.0339

AC:

1133

AN:

33454

American (AMR)

AF:

0.0148

AC:

660

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.0204

AC:

532

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.00552

AC:

476

AN:

86258

European-Finnish (FIN)

AF:

0.0154

AC:

822

AN:

53414

Middle Eastern (MID)

AF:

0.0281

AC:

162

AN:

5762

European-Non Finnish (NFE)

AF:

0.0145

AC:

16147

AN:

1111898

Other (OTH)

AF:

0.0160

AC:

969

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1190

2379

3569

4758

5948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

586

1172

1758

2344

2930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0209

AC:

3189

AN:

152252

Hom.:

Cov.:

AF XY:

0.0203

AC XY:

1512

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0320

AC:

1329

AN:

41534

American (AMR)

AF:

0.0182

AC:

278

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00456

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0162

AC:

172

AN:

10610

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0166

AC:

1128

AN:

68014

Other (OTH)

AF:

0.0359

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

169

338

508

677

846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0157

Hom.:

Bravo

AF:

0.0219

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0145

AC:

ESP6500AA

AF:

0.0279

AC:

123

ESP6500EA

AF:

0.0166

AC:

143

ExAC

AF:

0.0153

AC:

1854

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0168

EpiControl

AF:

0.0187

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Immunodeficiency, common variable, 7 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.58

(source)

DANN

Benign

0.85

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

PhyloP100

-2.0

GERP RS

-5.9

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over