chr12-93583178-A-G

Position:

• chr12-93583178-A-G

Variant summary

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

The ENST00000549510.1(SOCS2):​c.*132A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,850 control chromosomes in the GnomAD database, including 3,906 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 0.23 (3906 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOCS2 ENST00000549510.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

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]

SOCS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS2	XM_011538936.2	c.*132A>G		3_prime_UTR_variant	3/3		XP_011537238.1
SOCS2	XM_011538929.2	c.592-2510A>G		intron_variant			XP_011537231.1
SOCS2	XM_011538935.2	c.591+8005A>G		intron_variant			XP_011537237.1
SOCS2	XR_944810.2	n.970A>G		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOCS2	ENST00000549510.1	c.*132A>G		3_prime_UTR_variant	2/2	2		ENSP00000474888.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34196 AN: 151734 Hom.: 3902 Cov.: 30

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.202

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.225 AC: 34212 AN: 151850 Hom.: 3906 Cov.: 30 AF XY: 0.223 AC XY: 16528 AN XY: 74210

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.199

Alfa AF: 0.217 Hom.: 8551

Bravo AF: 0.229

Asia WGS AF: 0.192 AC: 671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.5
DANN	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3825199; hg19: chr12-93976954;