rs2115485

Variant names:

• chr9-90806972-C-T
• rs2115485
• NM_003177.7:c.-42+5079C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003177.7(SYK):​c.-42+5079C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,150 control chromosomes in the GnomAD database, including 4,202 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 0.23 (4202 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• Publications: 2 publications found

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]

SYK Gene-Disease associations (from GenCC):

• immunodeficiency 82 with systemic inflammation

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003177.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	NM_003177.7	MANE Select	c.-42+5079C>T		intron	N/A	NP_003168.2
	SYK	NM_001135052.4		c.-42+5079C>T		intron	N/A	NP_001128524.1
	SYK	NM_001174168.3		c.-42+4967C>T		intron	N/A	NP_001167639.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	ENST00000375754.9	TSL:1 MANE Select	c.-42+5079C>T		intron	N/A	ENSP00000364907.4
	SYK	ENST00000375747.5	TSL:1	c.-42+4967C>T		intron	N/A	ENSP00000364899.1
	SYK	ENST00000375751.8	TSL:1	c.-42+5079C>T		intron	N/A	ENSP00000364904.4

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35481 AN: 152032 Hom.: 4200 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.233 AC: 35504 AN: 152150 Hom.: 4202 Cov.: 33 AF XY: 0.232 AC XY: 17283 AN XY: 74392

African (AFR) AF: 0.217 AC: 9023 AN: 41498

American (AMR) AF: 0.225 AC: 3445 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3470

East Asian (EAS) AF: 0.174 AC: 904 AN: 5186

South Asian (SAS) AF: 0.216 AC: 1043 AN: 4826

European-Finnish (FIN) AF: 0.210 AC: 2222 AN: 10566

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16891 AN: 67994

Other (OTH) AF: 0.239 AC: 505 AN: 2110

Alfa AF: 0.246 Hom.: 2341

Bravo AF: 0.234

Asia WGS AF: 0.201 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.81
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2115485; hg19: chr9-93569254;