Variant 2-86790578-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001768.7(CD8A):c.153G>T(p.Thr51=) 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 464445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-86790578-C-A is described in Lovd as [Likely_benign].

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/exons	MANE	UniProt
CD8A	NM_001768.7 linkuse as main transcript	c.153G>T	p.Thr51=	synonymous_variant	2/6	ENST00000283635.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD8A	ENST00000283635.8 linkuse as main transcript	c.153G>T	p.Thr51=	synonymous_variant	2/6	1	NM_001768.7	P1	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

GnomAD3 exomes

AF:

0.00310

AC:

759

AN:

244788

Hom.:

AF XY:

0.00312

AC XY:

416

AN XY:

133346

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 SAS exome

AF:

0.000950

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

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00114

Gnomad4 FIN exome

AF:

0.00156

Gnomad4 NFE exome

AF:

0.00657

Gnomad4 OTH exome

AF:

0.00399

GnomAD4 genome

AF:

0.00305

AC:

464

AN:

152296

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

208

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00127

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00538

Gnomad4 OTH

AF:

0.000946

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	CD8A: BP4, BP7, BS2 -

Susceptibility to respiratory infections associated with CD8alpha chain mutation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

CD8A-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 03, 2019

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

DANN

Benign

0.65

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

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