rs2065583

Variant names:

• chr9-90830280-C-G
• rs2065583
• NM_003177.7:c.-41-13578C>G

Variant summary

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

The NM_003177.7(SYK):​c.-41-13578C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,262 control chromosomes in the GnomAD database, including 3,051 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 0.18 (3051 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.32
• Publications: 3 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), PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	NM_003177.7	MANE Select	c.-41-13578C>G		intron	N/A	NP_003168.2
	SYK	NM_001174167.3		c.-42+2701C>G		intron	N/A	NP_001167638.1	P43405-1
	SYK	NM_001135052.4		c.-41-13578C>G		intron	N/A	NP_001128524.1	P43405-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	ENST00000375754.9	TSL:1 MANE Select	c.-41-13578C>G		intron	N/A	ENSP00000364907.4	P43405-1
	SYK	ENST00000375746.1	TSL:1	c.-42+2701C>G		intron	N/A	ENSP00000364898.1	P43405-1
	SYK	ENST00000375747.5	TSL:1	c.-41-13578C>G		intron	N/A	ENSP00000364899.1	P43405-2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27989 AN: 152144 Hom.: 3051 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.00596

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.184 AC: 28000 AN: 152262 Hom.: 3051 Cov.: 33 AF XY: 0.180 AC XY: 13400 AN XY: 74444

African (AFR) AF: 0.297 AC: 12347 AN: 41538

American (AMR) AF: 0.133 AC: 2034 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 633 AN: 3472

East Asian (EAS) AF: 0.00597 AC: 31 AN: 5190

South Asian (SAS) AF: 0.153 AC: 738 AN: 4822

European-Finnish (FIN) AF: 0.103 AC: 1088 AN: 10604

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10335 AN: 68014

Other (OTH) AF: 0.167 AC: 352 AN: 2114

Alfa AF: 0.166 Hom.: 273

Bravo AF: 0.192

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.096
DANN	Benign	0.43
PhyloP100		-3.3
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: rs2065583; hg19: chr9-93592562;