Variant 1-116754851-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001767.5(CD2):c.282T>G(p.Ile94Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CD2
NM_001767.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00500

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD2	NM_001767.5 linkuse as main transcript	c.282T>G	p.Ile94Met	missense_variant	2/5	ENST00000369478.4
CD2	NM_001328609.2 linkuse as main transcript	c.282T>G	p.Ile94Met	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD2	ENST00000369478.4 linkuse as main transcript	c.282T>G	p.Ile94Met	missense_variant	2/5	1	NM_001767.5	P1
CD2	ENST00000369477.1 linkuse as main transcript	c.282T>G	p.Ile94Met	missense_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000280

AC:

AN:

250436

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1460488

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726662

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.282T>G (p.I94M) alteration is located in exon 2 (coding exon 2) of the CD2 gene. This alteration results from a T to G substitution at nucleotide position 282, causing the isoleucine (I) at amino acid position 94 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.17

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.016

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

0.93

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.4

N;D

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.69

MutPred

0.75

Loss of methylation at K95 (P = 0.0311);Loss of methylation at K95 (P = 0.0311);

MVP

0.76

MPC

0.26

ClinPred

0.67

GERP RS

-0.95

Varity_R

0.67

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over