chr2-86790433-G-A

Position:

chr2-86790433-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000283635.8(CD8A):c.298C>T(p.Leu100Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,614,138 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 38 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 38 hom. )

Consequence

CD8A
ENST00000283635.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.73

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009144366).

BP6

Variant 2-86790433-G-A is Benign according to our data. Variant chr2-86790433-G-A is described in ClinVar as [Benign]. Clinvar id is 464446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1736/152326) while in subpopulation AFR AF= 0.0386 (1606/41576). AF 95% confidence interval is 0.0371. There are 38 homozygotes in gnomad4. There are 802 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD8A	NM_001768.7 linkuse as main transcript	c.298C>T	p.Leu100Phe	missense_variant	2/6	ENST00000283635.8	NP_001759.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD8A	ENST00000283635.8 linkuse as main transcript	c.298C>T	p.Leu100Phe	missense_variant	2/6	1	NM_001768.7	ENSP00000283635	P1	P01732-1

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1734

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00301

AC:

756

AN:

251054

Hom.:

AF XY:

0.00222

AC XY:

302

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0422

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00129

AC:

1888

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

802

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0454

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.000132

Gnomad4 OTH exome

AF:

0.00219

GnomAD4 genome

AF:

0.0114

AC:

1736

AN:

152326

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

802

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0386

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.0133

ESP6500AA

AF:

0.0413

AC:

182

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00351

AC:

426

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Susceptibility to respiratory infections associated with CD8alpha chain mutation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.79

.;D;D;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.61

T;.;T;T

MetaRNN

Benign

0.0091

T;T;T;T

MetaSVM

Uncertain

-0.10

MutationAssessor

Uncertain

2.7

M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-4.0

D;D;D;D

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.46

MVP

0.99

MPC

1.4

ClinPred

0.027

GERP RS

4.7

Varity_R

0.78

gMVP

0.67

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.

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