1-207475111-G-T

Variant names:

Variant summary

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

The NM_001006658.3(CR2):c.2611G>T(p.Val871Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00493 in 1,612,780 control chromosomes in the GnomAD database, including 32 homozygotes. 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 (★★). Synonymous variant affecting the same amino acid position (i.e. V871V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 30 hom. )

Consequence

CR2
NM_001006658.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.600

Publications

5 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=0.00687328).

BP6

Variant 1-207475111-G-T is Benign according to our data. Variant chr1-207475111-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 439554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0033 (503/152280) while in subpopulation SAS AF = 0.00642 (31/4826). AF 95% confidence interval is 0.00465. There are 2 homozygotes in GnomAd4. There are 233 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 Unknown,AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR2	NM_001006658.3 link	c.2611G>T	p.Val871Leu	missense_variant	Exon 14 of 20	ENST00000367057.8	NP_001006659.1	P20023-3
CR2	NM_001877.5 link	c.2434G>T	p.Val812Leu	missense_variant	Exon 13 of 19		NP_001868.2	P20023-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8 link	c.2611G>T	p.Val871Leu	missense_variant	Exon 14 of 20	1	NM_001006658.3	ENSP00000356024.3		P20023-3

Frequencies

GnomAD3 genomes

AF:

0.00329

AC:

501

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00429

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00334

AC:

834

AN:

249514

AF XY:

0.00355

show subpopulations

Gnomad AFR exome

AF:

0.00302

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.000707

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000840

Gnomad NFE exome

AF:

0.00413

Gnomad OTH exome

AF:

0.00526

GnomAD4 exome

AF:

0.00510

AC:

7447

AN:

1460500

Hom.:

Cov.:

AF XY:

0.00514

AC XY:

3731

AN XY:

726466

show subpopulations

African (AFR)

AF:

0.00275

AC:

AN:

33442

American (AMR)

AF:

0.00148

AC:

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.00112

AC:

AN:

25998

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39686

South Asian (SAS)

AF:

0.00693

AC:

596

AN:

85994

European-Finnish (FIN)

AF:

0.000881

AC:

AN:

53342

Middle Eastern (MID)

AF:

0.00400

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00567

AC:

6296

AN:

1111312

Other (OTH)

AF:

0.00492

AC:

297

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

390

780

1169

1559

1949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.00330

AC:

503

AN:

152280

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

233

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00344

AC:

143

AN:

41546

American (AMR)

AF:

0.000850

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00642

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00431

AC:

293

AN:

68026

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00365

Hom.:

Bravo

AF:

0.00332

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00342

AC:

415

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00551

EpiControl

AF:

0.00480

ClinVar

Significance: Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 08, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CR2: BP4, BS2 -

Immunodeficiency, common variable, 7

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 11, 2023

Genome-Nilou Lab

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.19

T;.;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.0069

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.7

L;.;.

PhyloP100

0.60

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.079

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.012

B;B;B

Vest4

0.25

MutPred

0.61

Loss of catalytic residue at V812 (P = 0.0265);.;Loss of catalytic residue at V812 (P = 0.0265);

MVP

0.48

MPC

0.24

ClinPred

0.0033

GERP RS

0.43

Varity_R

0.056

gMVP

0.61

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over