Genetic Variant CR2:p.Ala1062Gly (chr1-207480050-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001006658.3(CR2):c.3185C>G(p.Ala1062Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1062E) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CR2
NM_001006658.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.173

Publications

32 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055491954).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR2	NM_001006658.3	MANE Select	c.3185C>G	p.Ala1062Gly	missense	Exon 18 of 20	NP_001006659.1	P20023-3
	CR2	NM_001877.5		c.3008C>G	p.Ala1003Gly	missense	Exon 17 of 19	NP_001868.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CR2	ENST00000367057.8	TSL:1 MANE Select	c.3185C>G	p.Ala1062Gly	missense	Exon 18 of 20	ENSP00000356024.3	P20023-3
CR2	ENST00000367058.7	TSL:1	c.3008C>G	p.Ala1003Gly	missense	Exon 17 of 19	ENSP00000356025.3	P20023-1
CR2	ENST00000367059.3	TSL:1	c.2822C>G	p.Ala941Gly	missense	Exon 16 of 18	ENSP00000356026.3	Q5SR47

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1458116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725596

African (AFR)

AF:

0.00

AC:

AN:

33340

American (AMR)

AF:

0.00

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108790

Other (OTH)

AF:

0.00

AC:

AN:

60238

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

148673

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.3

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.11

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.19

M_CAP

Benign

0.0041

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.17

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.020

REVEL

Benign

0.042

Sift

Uncertain

0.010

Sift4G

Benign

0.075

Polyphen

0.0

Vest4

0.060

MutPred

0.44

Gain of disorder (P = 0.0607)

MVP

0.21

MPC

0.18

ClinPred

0.065

GERP RS

-2.1

Varity_R

0.049

gMVP

0.45

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over