1-207480050-C-T

Variant names:

• chr1-207480050-C-T
• rs17617
• NM_001006658.3:c.3185C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001006658.3(CR2):​c.3185C>T​(p.Ala1062Val) 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. 15/22 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)
• Consequence: CR2 NM_001006658.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 32 publications found

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

ACMG classification

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=0.06462532).

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>T	p.Ala1062Val	missense	Exon 18 of 20	NP_001006659.1	P20023-3
	CR2	NM_001877.5		c.3008C>T	p.Ala1003Val	missense	Exon 17 of 19	NP_001868.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CR2	ENST00000367057.8	TSL:1 MANE Select	c.3185C>T	p.Ala1062Val	missense	Exon 18 of 20	ENSP00000356024.3	P20023-3
	CR2	ENST00000367058.7	TSL:1	c.3008C>T	p.Ala1003Val	missense	Exon 17 of 19	ENSP00000356025.3	P20023-1
	CR2	ENST00000367059.3	TSL:1	c.2822C>T	p.Ala941Val	missense	Exon 16 of 18	ENSP00000356026.3	Q5SR47

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 148673

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.17
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.053
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.044	D
Polyphen		0.0070	B
Vest4		0.10
MutPred		0.43		Loss of disorder (P = 0.0727)
MVP		0.22
MPC		0.16
ClinPred		0.091	T
GERP RS		-2.1
Varity_R		0.043
gMVP		0.44
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs17617; hg19: chr1-207653395;