dbSNP rs699738: CD2:p.His266Gln (chr1-116768525-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001767.5(CD2):c.798C>A(p.His266Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,613,782 control chromosomes in the GnomAD database, including 21,646 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.24 ( 7269 hom., cov: 31)

Exomes 𝑓: 0.11 ( 14377 hom. )

Consequence

CD2
NM_001767.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.481

Variant links:

Genes affected

CD2 (HGNC:1639): (CD2 molecule) The protein encoded by this gene is a surface antigen found on all peripheral blood T-cells. The encoded protein interacts with LFA3 (CD58) on antigen presenting cells to optimize immune recognition. A locus control region (LCR) has been found in the 3' flanking sequence of this gene. [provided by RefSeq, Jun 2016]

CD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3445467E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD2	NM_001767.5 link	c.798C>A	p.His266Gln	missense_variant	Exon 5 of 5	ENST00000369478.4	NP_001758.2	P06729Q53F96
CD2	NM_001328609.2 link	c.876C>A	p.His292Gln	missense_variant	Exon 5 of 5		NP_001315538.1	P06729Q53F96

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD2	ENST00000369478.4 link	c.798C>A	p.His266Gln	missense_variant	Exon 5 of 5	1	NM_001767.5	ENSP00000358490.3		P06729

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36464

AN:

151884

Hom.:

7232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0850

Gnomad OTH

AF:

0.219

GnomAD3 exomes

AF:

0.161

AC:

40457

AN:

251098

Hom.:

5157

AF XY:

0.147

AC XY:

19991

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.555

Gnomad AMR exome

AF:

0.206

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.281

Gnomad SAS exome

AF:

0.0933

Gnomad FIN exome

AF:

0.207

Gnomad NFE exome

AF:

0.0864

Gnomad OTH exome

AF:

0.153

GnomAD4 exome

AF:

0.110

AC:

161104

AN:

1461780

Hom.:

14377

Cov.:

AF XY:

0.108

AC XY:

78565

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.560

Gnomad4 AMR exome

AF:

0.213

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.290

Gnomad4 SAS exome

AF:

0.0945

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.0810

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.241

AC:

36557

AN:

152002

Hom.:

7269

Cov.:

AF XY:

0.243

AC XY:

18062

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.541

Gnomad4 AMR

AF:

0.210

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.282

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.0850

Gnomad4 OTH

AF:

0.222

Alfa

AF:

0.116

Hom.:

2438

Bravo

AF:

0.254

TwinsUK

AF:

0.0769

AC:

285

ALSPAC

AF:

0.0776

AC:

299

ESP6500AA

AF:

0.512

AC:

2258

ESP6500EA

AF:

0.0847

AC:

728

ExAC

AF:

0.163

AC:

19791

Asia WGS

AF:

0.268

AC:

931

AN:

3478

EpiCase

AF:

0.0909

EpiControl

AF:

0.0866

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.0

DANN

Benign

0.58

DEOGEN2

Benign

0.10

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.44

MetaRNN

Benign

0.000023

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Benign

0.55

Sift4G

Benign

0.57

Polyphen

0.085

Vest4

0.034

MutPred

0.041

Gain of MoRF binding (P = 0.1102);

MPC

0.038

ClinPred

0.0016

GERP RS

-3.0

Varity_R

0.052

gMVP

0.092

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over