chr2-86790539-G-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.192C>A(p.Ala64Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 1,613,474 control chromosomes in the GnomAD database, including 4,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A64A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.070 ( 407 hom., cov: 33)

Exomes 𝑓: 0.071 ( 4124 hom. )

Consequence

CD8A
NM_001768.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0350

Publications

5 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=-0.71).

BP6

Variant 2-86790539-G-T is Benign according to our data. Variant chr2-86790539-G-T is described in ClinVar as Benign. ClinVar VariationId is 402523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.035 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD8A	NM_001768.7 link	c.192C>A	p.Ala64Ala	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.192C>A	p.Ala64Ala	synonymous_variant	Exon 2 of 6	1	NM_001768.7	ENSP00000283635.3		P01732-1

Frequencies

GnomAD3 genomes

AF:

0.0698

AC:

10612

AN:

152118

Hom.:

407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0830

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0470

Gnomad ASJ

AF:

0.0542

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0580

Gnomad MID

AF:

0.0669

Gnomad NFE

AF:

0.0787

Gnomad OTH

AF:

0.0675

GnomAD2 exomes

AF:

0.0574

AC:

14110

AN:

245704

AF XY:

0.0562

show subpopulations

Gnomad AFR exome

AF:

0.0831

Gnomad AMR exome

AF:

0.0343

Gnomad ASJ exome

AF:

0.0584

Gnomad EAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.0591

Gnomad NFE exome

AF:

0.0810

Gnomad OTH exome

AF:

0.0568

GnomAD4 exome

AF:

0.0715

AC:

104406

AN:

1461238

Hom.:

4124

Cov.:

AF XY:

0.0699

AC XY:

50834

AN XY:

726956

show subpopulations

African (AFR)

AF:

0.0830

AC:

2780

AN:

33476

American (AMR)

AF:

0.0360

AC:

1609

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0561

AC:

1467

AN:

26128

East Asian (EAS)

AF:

0.000151

AC:

AN:

39700

South Asian (SAS)

AF:

0.0197

AC:

1701

AN:

86256

European-Finnish (FIN)

AF:

0.0589

AC:

3114

AN:

52910

Middle Eastern (MID)

AF:

0.0605

AC:

349

AN:

5766

European-Non Finnish (NFE)

AF:

0.0805

AC:

89536

AN:

1111902

Other (OTH)

AF:

0.0637

AC:

3844

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

5921

11842

17764

23685

29606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3246

6492

9738

12984

16230

<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:

10623

AN:

152236

Hom.:

407

Cov.:

AF XY:

0.0672

AC XY:

5000

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0831

AC:

3454

AN:

41548

American (AMR)

AF:

0.0469

AC:

718

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0542

AC:

188

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.0124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0580

AC:

616

AN:

10616

Middle Eastern (MID)

AF:

0.0582

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0787

AC:

5349

AN:

67994

Other (OTH)

AF:

0.0668

AC:

141

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

468

936

1403

1871

2339

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:

0.0593

Hom.:

148

Bravo

AF:

0.0689

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0767

EpiControl

AF:

0.0801

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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

-0.71

CADD

Benign

5.0

(source)

DANN

Benign

0.60

PhyloP100

-0.035

PromoterAI

-0.0024

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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