rs2780701

Variant names:

• chr9-90804999-A-G
• rs2780701
• NM_003177.7:c.-42+3106A>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.-42+3106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,838 control chromosomes in the GnomAD database, including 13,849 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 0.41 (13849 hom., cov: 32)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.-42+3106A>G		intron_variant	Intron 1 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.-42+3106A>G		intron_variant	Intron 1 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375747.5	c.-42+2994A>G		intron_variant	Intron 1 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.-42+3106A>G		intron_variant	Intron 1 of 12	1		ENSP00000364904.4
SYK	ENST00000476708.1	n.78+2960A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62621 AN: 151720 Hom.: 13853 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.413 AC: 62640 AN: 151838 Hom.: 13849 Cov.: 32 AF XY: 0.420 AC XY: 31163 AN XY: 74192

African (AFR) AF: 0.254 AC: 10509 AN: 41402

American (AMR) AF: 0.438 AC: 6689 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1589 AN: 3466

East Asian (EAS) AF: 0.618 AC: 3193 AN: 5170

South Asian (SAS) AF: 0.428 AC: 2064 AN: 4820

European-Finnish (FIN) AF: 0.599 AC: 6269 AN: 10474

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30901 AN: 67928

Other (OTH) AF: 0.421 AC: 888 AN: 2110

Alfa AF: 0.420 Hom.: 1753

Bravo AF: 0.399

Asia WGS AF: 0.481 AC: 1675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.53
DANN	Benign	0.46
PhyloP100		-1.1
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: rs2780701; hg19: chr9-93567281;