2-86858336-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004931.5(CD8B):​c.124G>A​(p.Glu42Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CD8B
NM_004931.5 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.372
Variant links:
Genes affected
CD8B (HGNC:1707): (CD8 subunit beta) The CD8 antigen is a cell surface glycoprotein found on most cytotoxic T lymphocytes that mediates efficient cell-cell interactions within the immune system. The CD8 antigen, acting as a coreceptor, and the T-cell receptor on the T lymphocyte recognize antigens displayed by an antigen presenting cell (APC) in the context of class I MHC molecules. The functional coreceptor is either a homodimer composed of two alpha chains, or a heterodimer composed of one alpha and one beta chain. Both alpha and beta chains share significant homology to immunoglobulin variable light chains. This gene encodes the CD8 beta chain isoforms. Multiple alternatively spliced transcript variants encoding distinct membrane associated or secreted isoforms have been described. A pseudogene, also located on chromosome 2, has been identified. [provided by RefSeq, May 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12482503).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD8BNM_004931.5 linkc.124G>A p.Glu42Lys missense_variant Exon 2 of 6 ENST00000390655.12 NP_004922.1 P10966-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD8BENST00000390655.12 linkc.124G>A p.Glu42Lys missense_variant Exon 2 of 6 1 NM_004931.5 ENSP00000375070.6 P10966-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152094
Hom.:
0
Cov.:
31
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:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000801
AC:
2
AN:
249626
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135048
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461658
Hom.:
0
Cov.:
38
AF XY:
0.0000151
AC XY:
11
AN XY:
727134
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152094
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 03, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.124G>A (p.E42K) alteration is located in exon 2 (coding exon 2) of the CD8B gene. This alteration results from a G to A substitution at nucleotide position 124, causing the glutamic acid (E) at amino acid position 42 to be replaced by a lysine (K). 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
Benign
0.14
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
7.6
DANN
Benign
0.94
DEOGEN2
Benign
0.12
.;.;.;.;T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.036
N
LIST_S2
Benign
0.73
T;T;T;T;T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.12
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.6
N;N;N;N;N;.
REVEL
Benign
0.056
Sift
Benign
0.068
T;T;T;T;T;.
Sift4G
Benign
0.37
T;T;T;T;T;T
Polyphen
0.035, 0.20, 0.47, 0.11
.;B;B;P;B;.
Vest4
0.30
MutPred
0.54
Gain of MoRF binding (P = 0.0022);Gain of MoRF binding (P = 0.0022);Gain of MoRF binding (P = 0.0022);Gain of MoRF binding (P = 0.0022);Gain of MoRF binding (P = 0.0022);Gain of MoRF binding (P = 0.0022);
MVP
0.37
MPC
0.68
ClinPred
0.064
T
GERP RS
0.24
Varity_R
0.058
gMVP
0.50

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.

Other links and lift over

dbSNP: rs753422558; hg19: chr2-87085459; COSMIC: COSV100514475; COSMIC: COSV100514475; API