chr2-97713815-TGTGTGCGG-T

Variant names:

• chr2-97713815-TGTGTGCGG-T
• rs72318626
• NM_001079.4:c.-100-100_-100-93delGTGTGCGG

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to ZAP70 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZAP70	NM_001079.4	MANE Select	c.-100-100_-100-93delGTGTGCGG		intron	N/A	NP_001070.2
	ZAP70	NM_001378594.1		c.-200_-193delGTGTGCGG		upstream_gene	N/A	NP_001365523.1	P43403-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZAP70	ENST00000264972.10	TSL:1 MANE Select	c.-100-100_-100-93delGTGTGCGG		intron	N/A	ENSP00000264972.5	P43403-1
	ZAP70	ENST00000698508.2		c.-200_-193delGTGTGCGG		5_prime_UTR	Exon 1 of 13	ENSP00000513759.1	P43403-1
	ZAP70	ENST00000885386.1		c.-88-100_-88-93delGTGTGCGG		intron	N/A	ENSP00000555445.1

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

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 10

South Asian (SAS) AF: 0.250 AC: 2 AN: 8

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.167 AC: 1 AN: 6

European-Non Finnish (NFE) AF: 0.0370 AC: 8 AN: 216

Other (OTH) AF: 0.00 AC: 0 AN: 8

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

African (AFR) AF: 0.00616 AC: 255 AN: 41406

American (AMR) AF: 0.0215 AC: 328 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3470

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5130

South Asian (SAS) AF: 0.110 AC: 529 AN: 4800

European-Finnish (FIN) AF: 0.0570 AC: 602 AN: 10568

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0336 AC: 2281 AN: 67896

Other (OTH) AF: 0.0213 AC: 45 AN: 2110

Alfa AF: 0.0266 Hom.: 8

Bravo AF: 0.0201

Asia WGS AF: 0.0390 AC: 137 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs72318626; hg19: chr2-98330278;