rs17617

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001006658.3(CR2):c.3185C>A(p.Ala1062Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,608,866 control chromosomes in the GnomAD database, including 597,269 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60237 hom., cov: 32)

Exomes 𝑓: 0.86 ( 537032 hom. )

Consequence

CR2
NM_001006658.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -0.173

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.1627176E-7).

BP6

Variant 1-207480050-C-A is Benign according to our data. Variant chr1-207480050-C-A is described in ClinVar as [Benign]. Clinvar id is 402562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-207480050-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CR2	NM_001006658.3 linkuse as main transcript	c.3185C>A	p.Ala1062Glu	missense_variant	18/20	ENST00000367057.8	NP_001006659.1
CR2	NM_001877.5 linkuse as main transcript	c.3008C>A	p.Ala1003Glu	missense_variant	17/19		NP_001868.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CR2	ENST00000367057.8 linkuse as main transcript	c.3185C>A	p.Ala1062Glu	missense_variant	18/20	1	NM_001006658.3	ENSP00000356024	P1	P20023-3

Frequencies

GnomAD3 genomes

AF:

0.887

AC:

134882

AN:

152116

Hom.:

60181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.972

Gnomad AMI

AF:

0.799

Gnomad AMR

AF:

0.878

Gnomad ASJ

AF:

0.827

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.926

Gnomad FIN

AF:

0.859

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.834

Gnomad OTH

AF:

0.879

GnomAD3 exomes

AF:

0.882

AC:

221217

AN:

250948

Hom.:

98033

AF XY:

0.878

AC XY:

119056

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.978

Gnomad AMR exome

AF:

0.916

Gnomad ASJ exome

AF:

0.827

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.922

Gnomad FIN exome

AF:

0.858

Gnomad NFE exome

AF:

0.838

Gnomad OTH exome

AF:

0.859

GnomAD4 exome

AF:

0.858

AC:

1249093

AN:

1456632

Hom.:

537032

Cov.:

AF XY:

0.858

AC XY:

622065

AN XY:

724876

show subpopulations

Gnomad4 AFR exome

AF:

0.979

Gnomad4 AMR exome

AF:

0.914

Gnomad4 ASJ exome

AF:

0.831

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.920

Gnomad4 FIN exome

AF:

0.858

Gnomad4 NFE exome

AF:

0.842

Gnomad4 OTH exome

AF:

0.865

GnomAD4 genome

AF:

0.887

AC:

134997

AN:

152234

Hom.:

60237

Cov.:

AF XY:

0.889

AC XY:

66171

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.972

Gnomad4 AMR

AF:

0.878

Gnomad4 ASJ

AF:

0.827

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.925

Gnomad4 FIN

AF:

0.859

Gnomad4 NFE

AF:

0.834

Gnomad4 OTH

AF:

0.880

Alfa

AF:

0.845

Hom.:

99800

Bravo

AF:

0.893

TwinsUK

AF:

0.849

AC:

3147

ALSPAC

AF:

0.844

AC:

3251

ESP6500AA

AF:

0.976

AC:

4299

ESP6500EA

AF:

0.829

AC:

7127

ExAC

AF:

0.883

AC:

107250

Asia WGS

AF:

0.967

AC:

3361

AN:

3478

EpiCase

AF:

0.829

EpiControl

AF:

0.840

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 98% of patients studied by a panel of primary immunodeficiencies. Number of patients: 93. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.81

DANN

Benign

0.27

DEOGEN2

Benign

0.099

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.15

T;T;T

MetaRNN

Benign

7.2e-7

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.90

N;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

1.4

N;N;N

REVEL

Benign

0.063

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.064

MPC

0.19

ClinPred

0.00086

GERP RS

-2.1

Varity_R

0.068

gMVP

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over