rs141831783

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_001006658.3(CR2):c.641G>A(p.Arg214His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000402 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R214C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

CR2
NM_001006658.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.639

Publications

9 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017165333).

BP6

Variant 1-207468806-G-A is Benign according to our data. Variant chr1-207468806-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 540320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000348 (53/152260) while in subpopulation EAS AF = 0.00463 (24/5182). AF 95% confidence interval is 0.00319. There are 0 homozygotes in GnomAd4. There are 28 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006658.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR2	NM_001006658.3	MANE Select	c.641G>A	p.Arg214His	missense	Exon 4 of 20	NP_001006659.1
	CR2	NM_001877.5		c.641G>A	p.Arg214His	missense	Exon 4 of 19	NP_001868.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CR2	ENST00000367057.8	TSL:1 MANE Select	c.641G>A	p.Arg214His	missense	Exon 4 of 20	ENSP00000356024.3
CR2	ENST00000367058.7	TSL:1	c.641G>A	p.Arg214His	missense	Exon 4 of 19	ENSP00000356025.3
CR2	ENST00000367059.3	TSL:1	c.641G>A	p.Arg214His	missense	Exon 4 of 18	ENSP00000356026.3

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00462

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000533

AC:

134

AN:

251228

AF XY:

0.000464

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00440

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000408

AC:

596

AN:

1461710

Hom.:

Cov.:

AF XY:

0.000425

AC XY:

309

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.000403

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00176

AC:

AN:

26132

East Asian (EAS)

AF:

0.00834

AC:

331

AN:

39696

South Asian (SAS)

AF:

0.000533

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000121

AC:

135

AN:

1111904

Other (OTH)

AF:

0.000331

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

122

162

203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000348

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41546

American (AMR)

AF:

0.000392

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.00463

AC:

AN:

5182

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68030

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000389

Hom.:

Bravo

AF:

0.000359

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000494

AC:

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency, common variable, 7

Benign:1

Dec 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.5

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.21

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.23

M_CAP

Benign

0.0050

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

-0.64

PrimateAI

Benign

0.18

PROVEAN

Benign

-1.0

REVEL

Benign

0.041

Sift

Benign

0.11

Sift4G

Benign

0.11

Polyphen

0.97

Vest4

0.051

MVP

0.28

MPC

0.20

ClinPred

0.0012

GERP RS

-6.5

Varity_R

0.019

gMVP

0.20

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over