1-207473553-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001006658.3(CR2):c.1987T>C(p.Ser663Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,609,678 control chromosomes in the GnomAD database, including 80,499 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9346 hom., cov: 32)

Exomes 𝑓: 0.31 ( 71153 hom. )

Consequence

CR2
NM_001006658.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.33

Publications

36 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=1.7824769E-4).

BP6

Variant 1-207473553-T-C is Benign according to our data. Variant chr1-207473553-T-C is described in ClinVar as [Benign]. Clinvar id is 402560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CR2	NM_001006658.3 link	c.1987T>C	p.Ser663Pro	missense_variant	Exon 11 of 20	ENST00000367057.8	NP_001006659.1	P20023-3
CR2	NM_001877.5 link	c.1979-248T>C		intron_variant	Intron 10 of 18		NP_001868.2	P20023-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8 link	c.1987T>C	p.Ser663Pro	missense_variant	Exon 11 of 20	1	NM_001006658.3	ENSP00000356024.3		P20023-3

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50782

AN:

151954

Hom.:

9317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.490

Gnomad AMI

AF:

0.206

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.318

GnomAD2 exomes

AF:

0.270

AC:

67724

AN:

250936

AF XY:

0.269

show subpopulations

Gnomad AFR exome

AF:

0.503

Gnomad AMR exome

AF:

0.169

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.230

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.282

GnomAD4 exome

AF:

0.305

AC:

444806

AN:

1457606

Hom.:

71153

Cov.:

AF XY:

0.303

AC XY:

219532

AN XY:

725296

show subpopulations

African (AFR)

AF:

0.498

AC:

16624

AN:

33368

American (AMR)

AF:

0.179

AC:

7994

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

7483

AN:

26114

East Asian (EAS)

AF:

0.121

AC:

4822

AN:

39688

South Asian (SAS)

AF:

0.235

AC:

20230

AN:

86178

European-Finnish (FIN)

AF:

0.228

AC:

12167

AN:

53398

Middle Eastern (MID)

AF:

0.323

AC:

1857

AN:

5750

European-Non Finnish (NFE)

AF:

0.321

AC:

355635

AN:

1108160

Other (OTH)

AF:

0.299

AC:

17994

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

16424

32849

49273

65698

82122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.334

AC:

50863

AN:

152072

Hom.:

9346

Cov.:

AF XY:

0.327

AC XY:

24289

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.490

AC:

20340

AN:

41478

American (AMR)

AF:

0.237

AC:

3618

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

965

AN:

3470

East Asian (EAS)

AF:

0.108

AC:

558

AN:

5178

South Asian (SAS)

AF:

0.230

AC:

1108

AN:

4820

European-Finnish (FIN)

AF:

0.226

AC:

2390

AN:

10588

Middle Eastern (MID)

AF:

0.307

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.308

AC:

20942

AN:

67964

Other (OTH)

AF:

0.315

AC:

665

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1673

3347

5020

6694

8367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.316

Hom.:

26868

Bravo

AF:

0.342

TwinsUK

AF:

0.319

AC:

1181

ALSPAC

AF:

0.326

AC:

1256

ESP6500AA

AF:

0.497

AC:

2188

ESP6500EA

AF:

0.316

AC:

2716

ExAC

AF:

0.281

AC:

34078

Asia WGS

AF:

0.193

AC:

669

AN:

3478

EpiCase

AF:

0.303

EpiControl

AF:

0.308

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 35% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Immunodeficiency, common variable, 7

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.29

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00081

LIST_S2

Benign

0.050

MetaRNN

Benign

0.00018

MetaSVM

Benign

-0.91

PhyloP100

-1.3

PrimateAI

Benign

0.29

PROVEAN

Benign

1.6

REVEL

Benign

0.076

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.069

MPC

0.21

ClinPred

0.0019

GERP RS

1.2

gMVP

0.52

Mutation Taster

=98/2

polymorphism (auto)

(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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1-207473553-T-C

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