rs699738

Variant names:

• chr1-116768525-C-A
• rs699738
• NM_001767.5:c.798C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-116768525-C-A
• chr1-116768525-C-G
• chr1-116768525-C-T

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001767.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2	NM_001767.5	MANE Select	c.798C>A	p.His266Gln	missense	Exon 5 of 5	NP_001758.2
	CD2	NM_001328609.2		c.876C>A	p.His292Gln	missense	Exon 5 of 5	NP_001315538.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD2	ENST00000369478.4	TSL:1 MANE Select	c.798C>A	p.His266Gln	missense	Exon 5 of 5	ENSP00000358490.3

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

GnomAD2 exomes AF: 0.161 AC: 40457 AN: 251098 AF XY: 0.147

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 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

African (AFR) AF: 0.560 AC: 18746 AN: 33478

American (AMR) AF: 0.213 AC: 9501 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2859 AN: 26136

East Asian (EAS) AF: 0.290 AC: 11500 AN: 39690

South Asian (SAS) AF: 0.0945 AC: 8149 AN: 86252

European-Finnish (FIN) AF: 0.197 AC: 10513 AN: 53406

Middle Eastern (MID) AF: 0.151 AC: 873 AN: 5768

European-Non Finnish (NFE) AF: 0.0810 AC: 90085 AN: 1111958

Other (OTH) AF: 0.147 AC: 8878 AN: 60392

GnomAD4 genome AF: 0.241 AC: 36557 AN: 152002 Hom.: 7269 Cov.: 31 AF XY: 0.243 AC XY: 18062 AN XY: 74310

African (AFR) AF: 0.541 AC: 22374 AN: 41376

American (AMR) AF: 0.210 AC: 3202 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3464

East Asian (EAS) AF: 0.282 AC: 1456 AN: 5164

South Asian (SAS) AF: 0.108 AC: 521 AN: 4822

European-Finnish (FIN) AF: 0.211 AC: 2232 AN: 10584

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0850 AC: 5782 AN: 68000

Other (OTH) AF: 0.222 AC: 468 AN: 2112

Alfa AF: 0.126 Hom.: 4123

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 v4.9

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
PhyloP100		-0.48
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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