rs699738

chr1-116768525-C-Achr1-116768525-C-Gchr1-116768525-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.24 (7269 hom., cov: 31)
  • Exomes 𝑓: 0.11 (14377 hom.)
• Consequence: CD2 NM_001767.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

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]

ACMG classification

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/exons	MANE	UniProt
CD2	NM_001767.5	c.798C>A	p.His266Gln	missense_variant	5/5	ENST00000369478.4
CD2	NM_001328609.2	c.876C>A	p.His292Gln	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD2	ENST00000369478.4	c.798C>A	p.His266Gln	missense_variant	5/5	1	NM_001767.5	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36464 AN: 151884 Hom.: 7232 Cov.: 31

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

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.: 32 AF XY: 0.108 AC XY: 78565 AN XY: 727200

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.: 31 AF XY: 0.243 AC XY: 18062 AN XY: 74310

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	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	9.0
Dann	Benign	0.58
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.000023	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.14
Sift	Benign	0.55	T
Sift4G	Benign	0.57	T
Polyphen		0.085	B
Vest4		0.034
MutPred		0.041		Gain of MoRF binding (P = 0.1102);
MPC		0.038
ClinPred		0.0016	T
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

Other links and lift over

dbSNP: rs699738; hg19: chr1-117311147; COSMIC: COSV65643860;