2-86790578-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001768.7(CD8A):c.153G>T(p.Thr51Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 1,612,602 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 28 hom. )

Consequence

CD8A
NM_001768.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.22

Publications

1 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 2-86790578-C-A is Benign according to our data. Variant chr2-86790578-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 464445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.22 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD8A	NM_001768.7 link	c.153G>T	p.Thr51Thr	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.153G>T	p.Thr51Thr	synonymous_variant	Exon 2 of 6	1	NM_001768.7	ENSP00000283635.3		P01732-1

Frequencies

GnomAD3 genomes

AF:

0.00306

AC:

466

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00541

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00310

AC:

759

AN:

244788

AF XY:

0.00312

show subpopulations

Gnomad AFR exome

AF:

0.000835

Gnomad AMR exome

AF:

0.000638

Gnomad ASJ exome

AF:

0.000703

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.00582

Gnomad OTH exome

AF:

0.00314

GnomAD4 exome

AF:

0.00534

AC:

7802

AN:

1460306

Hom.:

Cov.:

AF XY:

0.00524

AC XY:

3809

AN XY:

726522

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33476

American (AMR)

AF:

0.000514

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.000498

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00114

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00156

AC:

AN:

52070

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00657

AC:

7310

AN:

1111890

Other (OTH)

AF:

0.00399

AC:

241

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

501

1002

1504

2005

2506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

280

560

840

1120

1400

<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:

0.00305

AC:

464

AN:

152296

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

208

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00127

AC:

AN:

41582

American (AMR)

AF:

0.00183

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000866

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.000622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000754

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00538

AC:

366

AN:

68006

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

101

126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00418

Hom.:

Bravo

AF:

0.00300

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00403

EpiControl

AF:

0.00545

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CD8A: BP4, BP7, BS2 -

Susceptibility to respiratory infections associated with CD8alpha chain mutation

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CD8A-related disorder

Benign:1

Jul 03, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.80

(source)

DANN

Benign

0.65

PhyloP100

-3.2

PromoterAI

0.038

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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