2-97748701-G-C

Position:

• chr2-97748701-G-C

Variant summary

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

The XM_047445775.1(ZAP70):​c.*7292G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,126 control chromosomes in the GnomAD database, including 8,128 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 0.29 (8128 hom., cov: 31)
• Consequence: ZAP70 XM_047445775.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZAP70	XM_047445775.1	c.*7292G>C		3_prime_UTR_variant	14/14		XP_047301731.1
ZAP70	XM_047445776.1	c.*7292G>C		3_prime_UTR_variant	14/14		XP_047301732.1
ZAP70	XR_007081582.1	n.7748G>C		non_coding_transcript_exon_variant	15/15
		n.97748701G>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44068 AN: 152008 Hom.: 8129 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.00867

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.290 AC: 44069 AN: 152126 Hom.: 8128 Cov.: 31 AF XY: 0.294 AC XY: 21837 AN XY: 74370

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.00869

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.243

Alfa AF: 0.239 Hom.: 742

Bravo AF: 0.257

Asia WGS AF: 0.0880 AC: 307 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	0.71
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17488897; hg19: chr2-98365164;