XM_011538936.2:c.*1682G>T

Variant names:

• chr12-93584728-G-T
• rs11107116
• XM_011538936.2:c.*1682G>T

Variant summary

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

The XM_011538936.2(SOCS2):​c.*1682G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 151,884 control chromosomes in the GnomAD database, including 2,842 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 (2842 hom., cov: 32)
• Consequence: SOCS2 XM_011538936.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOCS2	XM_011538936.2	c.*1682G>T		3_prime_UTR_variant	Exon 3 of 3		XP_011537238.1
SOCS2	XM_011538929.2	c.592-960G>T		intron_variant	Intron 2 of 2		XP_011537231.1
SOCS2	XM_011538935.2	c.591+9555G>T		intron_variant	Intron 2 of 2		XP_011537237.1
SOCS2	XR_944810.2	n.1081-960G>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27482 AN: 151768 Hom.: 2838 Cov.: 32

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.181 AC: 27487 AN: 151884 Hom.: 2842 Cov.: 32 AF XY: 0.181 AC XY: 13418 AN XY: 74200

Gnomad4 AFR AF: 0.0816

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.170

Alfa AF: 0.191 Hom.: 2395

Bravo AF: 0.178

Asia WGS AF: 0.182 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.7
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11107116; hg19: chr12-93978504;