rs2242545

Variant names:

• chr14-22455202-G-A
• rs2242545

Your query was ambiguous. Multiple possible variants found:

• chr14-22455202-G-A
• chr14-22455202-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.258 in 762,588 control chromosomes in the GnomAD database, including 27,558 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (4027 hom., cov: 25)
  • Exomes 𝑓: 0.27 (23531 hom.)
• Consequence: TRA intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

TRA (HGNC:12027):

TRD (HGNC:12252):

TRD-AS1 (HGNC:56197): (TRD antisense RNA 1)

TRDJ4 (HGNC:12260): (T cell receptor delta joining 4) T cell receptors recognize foreign antigens which have been processed as small peptides and bound to major histocompatibility complex (MHC) molecules at the surface of antigen presenting cells (APC). Each T cell receptor is a dimer consisting of one alpha and one beta chain or one delta and one gamma chain. In a single cell, the T cell receptor loci are rearranged and expressed in the order delta, gamma, beta, and alpha. If both delta and gamma rearrangements produce functional chains, the cell expresses delta and gamma. If not, the cell proceeds to rearrange the beta and alpha loci. This region represents the germline organization of the T cell receptor alpha and delta loci. Both the alpha and delta loci include V (variable), J (joining), and C (constant) segments and the delta locus also includes diversity (D) segments. The delta locus is situated within the alpha locus, between the alpha V and J segments. During T cell development, the delta chain is synthesized by a recombination event at the DNA level joining a D segment with a J segment; a V segment is then joined to the D-J gene. The alpha chain is synthesized by recombination joining a single V segment with a J segment. For both chains, the C segment is later joined by splicing at the RNA level. Recombination of many different V segments with several J segments provides a wide range of antigen recognition. Additional diversity is attained by junctional diversity, resulting from the random additional of nucleotides by terminal deoxynucleotidyltransferase. Five variable segments can be used in either alpha or delta chains and are described by TRAV/DV symbols. Several V and J segments of the alpha locus are known to be incapable of encoding a protein and are considered pseudogenes. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRA		n.22455202G>A		intragenic_variant
TRD		n.22455202G>A		intragenic_variant
TRD-AS1	NR_148361.1	n.225+26039C>T		intron_variant	Intron 2 of 4
TRDJ4	unassigned_transcript_2241	c.-49G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRD-AS1	ENST00000514473.2	n.225+26039C>T		intron_variant	Intron 2 of 2	2
TRDJ4	ENST00000390474.1	c.-49G>A		upstream_gene_variant		6		ENSP00000452040.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31380 AN: 150726 Hom.: 4025 Cov.: 25

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.213

GnomAD3 exomes AF: 0.249 AC: 57761 AN: 231592 Hom.: 7921 AF XY: 0.261 AC XY: 33000 AN XY: 126620

Gnomad AFR exome AF: 0.0566

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.289

Gnomad EAS exome AF: 0.152

Gnomad SAS exome AF: 0.343

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.281

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.271 AC: 165512 AN: 611744 Hom.: 23531 Cov.: 0 AF XY: 0.277 AC XY: 92645 AN XY: 334378

Gnomad4 AFR exome AF: 0.0656

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.342

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.208 AC: 31398 AN: 150844 Hom.: 4027 Cov.: 25 AF XY: 0.211 AC XY: 15501 AN XY: 73632

Gnomad4 AFR AF: 0.0608

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.218

Alfa AF: 0.269 Hom.: 8752

Bravo AF: 0.191

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.015
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2242545; hg19: chr14-22924194; COSMIC: COSV66604807;