2-86788510-T-TGA

Position:

• chr2-86788510-T-TGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001768.7(CD8A):​c.656+18_656+19dupTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 1,604,790 control chromosomes in the GnomAD database, including 526,822 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (51901 hom., cov: 0)
  • Exomes 𝑓: 0.81 (474921 hom.)
• Consequence: CD8A NM_001768.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.437

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-86788510-T-TGA is Benign according to our data. Variant chr2-86788510-T-TGA is described in ClinVar as [Benign]. Clinvar id is 1168126.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD8A	NM_001768.7	c.656+18_656+19dupTC		intron_variant		ENST00000283635.8	NP_001759.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD8A	ENST00000283635.8	c.656+18_656+19dupTC		intron_variant		1	NM_001768.7	ENSP00000283635.3

Frequencies

GnomAD3 genomes AF: 0.825 AC: 124988 AN: 151584 Hom.: 51845 Cov.: 0

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.803

GnomAD3 exomes AF: 0.795 AC: 197921 AN: 248850 Hom.: 79607 AF XY: 0.786 AC XY: 105613 AN XY: 134318

Gnomad AFR exome AF: 0.890

Gnomad AMR exome AF: 0.797

Gnomad ASJ exome AF: 0.733

Gnomad EAS exome AF: 0.989

Gnomad SAS exome AF: 0.638

Gnomad FIN exome AF: 0.770

Gnomad NFE exome AF: 0.803

Gnomad OTH exome AF: 0.776

GnomAD4 exome AF: 0.806 AC: 1171187 AN: 1453088 Hom.: 474921 Cov.: 30 AF XY: 0.800 AC XY: 578627 AN XY: 723134

Gnomad4 AFR exome AF: 0.892

Gnomad4 AMR exome AF: 0.795

Gnomad4 ASJ exome AF: 0.737

Gnomad4 EAS exome AF: 0.977

Gnomad4 SAS exome AF: 0.641

Gnomad4 FIN exome AF: 0.774

Gnomad4 NFE exome AF: 0.814

Gnomad4 OTH exome AF: 0.799

GnomAD4 genome AF: 0.825 AC: 125100 AN: 151702 Hom.: 51901 Cov.: 0 AF XY: 0.818 AC XY: 60588 AN XY: 74106

Gnomad4 AFR AF: 0.891

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.805

Alfa AF: 0.803 Hom.: 8950

Bravo AF: 0.834

Asia WGS AF: 0.817 AC: 2840 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10684959; hg19: chr2-87015633;