9-90844394-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003177.7(SYK):c.417+79A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,404,514 control chromosomes in the GnomAD database, including 78,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7098 hom., cov: 34)
  • Exomes 𝑓: 0.34 (71802 hom.)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.29

Genes affected

SYK (HGNC:11491): (spleen associated tyrosine kinase) This gene encodes a member of the family of non-receptor type Tyr protein kinases. This protein is widely expressed in hematopoietic cells and is involved in coupling activated immunoreceptors to downstream signaling events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis. It is thought to be a modulator of epithelial cell growth and a potential tumour suppressor in human breast carcinomas. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-90844394-A-G is Benign according to our data. Variant chr9-90844394-A-G is described in ClinVar as [Benign]. Clinvar id is 2688110.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYK	NM_003177.7	c.417+79A>G		intron_variant		ENST00000375754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYK	ENST00000375754.9	c.417+79A>G		intron_variant		1	NM_003177.7	P1
SYK	ENST00000375746.1	c.417+79A>G		intron_variant		1		P1
SYK	ENST00000375747.5	c.417+79A>G		intron_variant		1
SYK	ENST00000375751.8	c.417+79A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45778 AN: 152068 Hom.: 7082 Cov.: 34

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.339 AC: 424375 AN: 1252328 Hom.: 71802 AF XY: 0.340 AC XY: 207640 AN XY: 611280

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.329

GnomAD4 genome AF: 0.301 AC: 45843 AN: 152186 Hom.: 7098 Cov.: 34 AF XY: 0.303 AC XY: 22548 AN XY: 74426

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.279

Alfa AF: 0.213 Hom.: 592

Bravo AF: 0.287

Asia WGS AF: 0.353 AC: 1224 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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 53% of patients studied by a panel of primary immunodeficiencies. Number of patients: 50. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.28
Dann	Benign	0.59

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: rs2278275; hg19: chr9-93606676; COSMIC: COSV65326129; COSMIC: COSV65326129;