chr12-93573027-G-A

Variant names:

• chr12-93573027-G-A
• rs769795840
• NM_001270471.2:c.130G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001270471.2(SOCS2):​c.130G>A​(p.Gly44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,412,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SOCS2 NM_001270471.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0930
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05431038).
• BP6: Variant 12-93573027-G-A is Benign according to our data. Variant chr12-93573027-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3321393.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270471.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS2	NM_001270471.2	MANE Select	c.130G>A	p.Gly44Ser	missense	Exon 1 of 2	NP_001257400.1	O14508
	SOCS2	NM_001270467.2		c.130G>A	p.Gly44Ser	missense	Exon 2 of 3	NP_001257396.1	O14508
	SOCS2	NM_001270468.2		c.130G>A	p.Gly44Ser	missense	Exon 2 of 3	NP_001257397.1	O14508

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS2	ENST00000551556.2	TSL:1 MANE Select	c.130G>A	p.Gly44Ser	missense	Exon 1 of 2	ENSP00000449227.1	O14508
	SOCS2	ENST00000340600.6	TSL:1	c.130G>A	p.Gly44Ser	missense	Exon 2 of 3	ENSP00000339428.2	O14508
	SOCS2	ENST00000549122.5	TSL:1	c.130G>A	p.Gly44Ser	missense	Exon 2 of 3	ENSP00000447161.1	O14508

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 163314 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1412972 Hom.: 0 Cov.: 31 AF XY: 0.00000286 AC XY: 2 AN XY: 699394

African (AFR) AF: 0.00 AC: 0 AN: 32690

American (AMR) AF: 0.00 AC: 0 AN: 38354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25426

East Asian (EAS) AF: 0.00 AC: 0 AN: 37556

South Asian (SAS) AF: 0.0000371 AC: 3 AN: 80946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091812

Other (OTH) AF: 0.00 AC: 0 AN: 58780

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000861 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.26	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-0.093
PrimateAI	Benign	0.47	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.027
Sift	Benign	0.52	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.069
MutPred		0.39		Gain of phosphorylation at G44 (P = 0.049)
MVP		0.21
MPC		0.60
ClinPred		0.059	T
GERP RS		-2.2
PromoterAI		-0.0091	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.5
Varity_R		0.14
gMVP		0.51
Mutation Taster		=77/23	polymorphism

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: rs769795840; hg19: chr12-93966803;