rs10492321

Positions:

• chr12-93586312-T-A
• chr12-93586312-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011538935.2(SOCS2):​c.591+11139T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,238 control chromosomes in the GnomAD database, including 3,215 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 0.20 (3215 hom., cov: 33)
• Consequence: SOCS2 XM_011538935.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

Genes affected

SOCS2 (HGNC:19382): (suppressor of cytokine signaling 2) This gene encodes a member of the suppressor of cytokine signaling (SOCS) family. SOCS family members are cytokine-inducible negative regulators of cytokine receptor signaling via the Janus kinase/signal transducer and activation of transcription pathway (the JAK/STAT pathway). SOCS family proteins interact with major molecules of signaling complexes to block further signal transduction, in part, by proteasomal depletion of receptors or signal-transducing proteins via ubiquitination. The expression of this gene can be induced by a subset of cytokines, including erythropoietin, GM-CSF, IL10, interferon (IFN)-gamma and by cytokine receptors such as growth horomone receptor. The protein encoded by this gene interacts with the cytoplasmic domain of insulin-like growth factor-1 receptor (IGF1R) and is thought to be involved in the regulation of IGF1R mediated cell signaling. This gene has pseudogenes on chromosomes 20 and 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS2	XM_011538935.2	c.591+11139T>A		intron_variant			XP_011537237.1
		n.93586312T>A		intergenic_region
SOCS2	XM_011538929.2	c.*553T>A		downstream_gene_variant			XP_011537231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30568 AN: 152120 Hom.: 3211 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.201 AC: 30593 AN: 152238 Hom.: 3215 Cov.: 33 AF XY: 0.200 AC XY: 14911 AN XY: 74438

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.184

Alfa AF: 0.220 Hom.: 482

Bravo AF: 0.201

Asia WGS AF: 0.192 AC: 669 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.3
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10492321; hg19: chr12-93980088;