rs768775

chr12-93574421-T-C

Variant summary

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

The NM_001270471.2(SOCS2):c.140-301T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 241,792 control chromosomes in the GnomAD database, including 5,714 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 0.19 (3411 hom., cov: 31)
  • Exomes 𝑓: 0.20 (2303 hom.)
• Consequence: SOCS2 NM_001270471.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOCS2	NM_001270471.2	c.140-301T>C		intron_variant		ENST00000551556.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOCS2	ENST00000551556.2	c.140-301T>C		intron_variant		1	NM_001270471.2	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29137 AN: 151712 Hom.: 3404 Cov.: 31

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.205 AC: 18437 AN: 89962 Hom.: 2303 Cov.: 0 AF XY: 0.203 AC XY: 9347 AN XY: 45980

Gnomad4 AFR exome AF: 0.0903

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.455

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.289

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.192 AC: 29159 AN: 151830 Hom.: 3411 Cov.: 31 AF XY: 0.197 AC XY: 14650 AN XY: 74192

Gnomad4 AFR AF: 0.0896

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.177

Alfa AF: 0.203 Hom.: 434

Bravo AF: 0.191

Asia WGS AF: 0.237 AC: 824 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.66
Dann	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs768775; hg19: chr12-93968197;