2-97713815-TGTGTGCGG-T

Position:

• chr2-97713815-TGTGTGCGG-T

Variant summary

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

The NM_001079.4(ZAP70):​c.-100-100_-100-93delGTGTGCGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 152,106 control chromosomes in the GnomAD database, including 93 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (93 hom., cov: 32)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: ZAP70 NM_001079.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.904

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]

ZAP70 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-97713815-TGTGTGCGG-T is Benign according to our data. Variant chr2-97713815-TGTGTGCGG-T is described in ClinVar as [Benign]. Clinvar id is 1302752.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZAP70	NM_001079.4	c.-100-100_-100-93delGTGTGCGG		intron_variant		ENST00000264972.10	NP_001070.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZAP70	ENST00000264972.10	c.-100-100_-100-93delGTGTGCGG		intron_variant		1	NM_001079.4	ENSP00000264972.5
ZAP70	ENST00000698508	c.-200_-193delGTGTGCGG		5_prime_UTR_variant	1/13			ENSP00000513759.1
ZAP70	ENST00000483781.5	n.94-100_94-93delGTGTGCGG		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4102 AN: 151728 Hom.: 92 Cov.: 32

Gnomad AFR AF: 0.00618

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0570

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.0211

GnomAD4 exome AF: 0.0423 AC: 11 AN: 260 Hom.: 0 AF XY: 0.0435 AC XY: 8 AN XY: 184

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0370

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0271 AC: 4108 AN: 151846 Hom.: 93 Cov.: 32 AF XY: 0.0298 AC XY: 2215 AN XY: 74220

Gnomad4 AFR AF: 0.00616

Gnomad4 AMR AF: 0.0215

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0570

Gnomad4 NFE AF: 0.0336

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0266 Hom.: 8

Bravo AF: 0.0201

Asia WGS AF: 0.0390 AC: 137 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2021

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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: rs72318626; hg19: chr2-98330278;