chr2-86790452-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001768.7(CD8A):c.279G>A(p.Arg93Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 1,614,066 control chromosomes in the GnomAD database, including 4,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 406 hom., cov: 32)

Exomes 𝑓: 0.071 ( 4115 hom. )

Consequence

CD8A
NM_001768.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.158

Publications

7 publications found

Variant links:

Genes affected

CD8A (HGNC:1706): (CD8 subunit alpha) 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 acts as a coreceptor with the T-cell receptor on the T lymphocyte to recognize antigens displayed by an antigen presenting cell in the context of class I MHC molecules. The coreceptor functions as either a homodimer composed of two alpha chains or as 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 alpha chain. Multiple transcript variants encoding different isoforms have been found for this gene. The major protein isoforms of this gene differ by the presence or absence of a transmembrane domain and thus differ in being a membrane-anchored or secreted protein. [provided by RefSeq, May 2020]

CD8A Gene-Disease associations (from GenCC):

susceptibility to respiratory infections associated with CD8alpha chain mutation
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

CD8A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 2-86790452-C-T is Benign according to our data. Variant chr2-86790452-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 402522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-86790452-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 402522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-86790452-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 402522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-86790452-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 402522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-86790452-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 402522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-86790452-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 402522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-86790452-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 402522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-86790452-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 402522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-86790452-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 402522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.158 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD8A	NM_001768.7 link	c.279G>A	p.Arg93Arg	synonymous_variant	Exon 2 of 6	ENST00000283635.8	NP_001759.3	P01732-1Q6ZVS2Q8TAW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD8A	ENST00000283635.8 link	c.279G>A	p.Arg93Arg	synonymous_variant	Exon 2 of 6	1	NM_001768.7	ENSP00000283635.3		P01732-1

Frequencies

GnomAD3 genomes

AF:

0.0698

AC:

10620

AN:

152200

Hom.:

406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0830

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0469

Gnomad ASJ

AF:

0.0541

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0126

Gnomad FIN

AF:

0.0578

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0787

Gnomad OTH

AF:

0.0673

GnomAD2 exomes

AF:

0.0573

AC:

14392

AN:

250974

AF XY:

0.0561

show subpopulations

Gnomad AFR exome

AF:

0.0809

Gnomad AMR exome

AF:

0.0343

Gnomad ASJ exome

AF:

0.0585

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0589

Gnomad NFE exome

AF:

0.0803

Gnomad OTH exome

AF:

0.0565

GnomAD4 exome

AF:

0.0714

AC:

104343

AN:

1461748

Hom.:

4115

Cov.:

AF XY:

0.0699

AC XY:

50815

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.0830

AC:

2778

AN:

33476

American (AMR)

AF:

0.0360

AC:

1609

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0561

AC:

1467

AN:

26136

East Asian (EAS)

AF:

0.000151

AC:

AN:

39700

South Asian (SAS)

AF:

0.0197

AC:

1700

AN:

86256

European-Finnish (FIN)

AF:

0.0587

AC:

3132

AN:

53382

Middle Eastern (MID)

AF:

0.0604

AC:

348

AN:

5766

European-Non Finnish (NFE)

AF:

0.0805

AC:

89463

AN:

1111912

Other (OTH)

AF:

0.0636

AC:

3840

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

5715

11429

17144

22858

28573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3244

6488

9732

12976

16220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0698

AC:

10631

AN:

152318

Hom.:

406

Cov.:

AF XY:

0.0671

AC XY:

5001

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0832

AC:

3458

AN:

41566

American (AMR)

AF:

0.0469

AC:

717

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0541

AC:

188

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0122

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0578

AC:

614

AN:

10616

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0787

AC:

5356

AN:

68026

Other (OTH)

AF:

0.0666

AC:

141

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

498

996

1495

1993

2491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0566

Hom.:

Bravo

AF:

0.0689

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0767

EpiControl

AF:

0.0801

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 23, 2025

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Susceptibility to respiratory infections associated with CD8alpha chain mutation

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.6

(source)

DANN

Benign

0.65

PhyloP100

-0.16

PromoterAI

0.0080

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over