chr2-97713755-A-G

Position:

• chr2-97713755-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001079.4(ZAP70):​c.-101+81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,352 control chromosomes in the GnomAD database, including 36,551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (36474 hom., cov: 32)
  • Exomes 𝑓: 0.71 (77 hom.)
• Consequence: ZAP70 NM_001079.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.100

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-97713755-A-G is Benign according to our data. Variant chr2-97713755-A-G is described in ClinVar as [Benign]. Clinvar id is 1226084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZAP70	NM_001079.4	c.-101+81A>G		intron_variant		ENST00000264972.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZAP70	ENST00000264972.10	c.-101+81A>G		intron_variant		1	NM_001079.4	P1
ZAP70	ENST00000483781.5	n.93+81A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103868 AN: 151948 Hom.: 36455 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.687

GnomAD4 exome AF: 0.711 AC: 202 AN: 284 Hom.: 77 Cov.: 0 AF XY: 0.733 AC XY: 151 AN XY: 206

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.757

Gnomad4 OTH exome AF: 0.643

GnomAD4 genome AF: 0.683 AC: 103928 AN: 152068 Hom.: 36474 Cov.: 32 AF XY: 0.676 AC XY: 50240 AN XY: 74340

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.682

Alfa AF: 0.724 Hom.: 5138

Bravo AF: 0.675

Asia WGS AF: 0.386 AC: 1346 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 77% of patients studied by a panel of primary immunodeficiencies. Number of patients: 73. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.4
DANN	Benign	0.62

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: rs2276644; hg19: chr2-98330218;