2-97714363-C-T

Position:

• chr2-97714363-C-T

Variant summary

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

The NM_001079.4(ZAP70):​c.-22+369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,176 control chromosomes in the GnomAD database, including 8,528 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 0.30 (8528 hom., cov: 33)
• Consequence: ZAP70 NM_001079.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

Genes affected

ZAP70 (HGNC:12858): (zeta chain of T cell receptor associated protein kinase 70) This gene encodes an enzyme belonging to the protein tyrosine kinase family, and it plays a role in T-cell development and lymphocyte activation. This enzyme, which is phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation, functions in the initial step of TCR-mediated signal transduction in combination with the Src family kinases, Lck and Fyn. This enzyme is also essential for thymocyte development. Mutations in this gene cause selective T-cell defect, a severe combined immunodeficiency disease characterized by a selective absence of CD8-positive T-cells. Two transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZAP70	NM_001079.4	c.-22+369C>T		intron_variant		ENST00000264972.10	NP_001070.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZAP70	ENST00000264972.10	c.-22+369C>T		intron_variant		1	NM_001079.4	ENSP00000264972	P1
ZAP70	ENST00000698508.1	c.-22+369C>T		intron_variant				ENSP00000513759	P1
ZAP70	ENST00000483781.5	n.172+369C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45714 AN: 152056 Hom.: 8528 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.300 AC: 45716 AN: 152176 Hom.: 8528 Cov.: 33 AF XY: 0.304 AC XY: 22590 AN XY: 74426

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.256

Alfa AF: 0.339 Hom.: 4521

Bravo AF: 0.271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs1020396; hg19: chr2-98330826;