chr12-93572946-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001270471.2(SOCS2):c.49C>T(p.Arg17Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000427 in 1,569,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R17P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

SOCS2
NM_001270471.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.962

Publications

0 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14371541).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SOCS2	NM_001270471.2	MANE Select	c.49C>T	p.Arg17Trp	missense	Exon 1 of 2	NP_001257400.1	O14508
SOCS2	NM_001270467.2		c.49C>T	p.Arg17Trp	missense	Exon 2 of 3	NP_001257396.1	O14508
SOCS2	NM_001270468.2		c.49C>T	p.Arg17Trp	missense	Exon 2 of 3	NP_001257397.1	O14508

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SOCS2	ENST00000551556.2	TSL:1 MANE Select	c.49C>T	p.Arg17Trp	missense	Exon 1 of 2	ENSP00000449227.1	O14508
SOCS2	ENST00000340600.6	TSL:1	c.49C>T	p.Arg17Trp	missense	Exon 2 of 3	ENSP00000339428.2	O14508
SOCS2	ENST00000549122.5	TSL:1	c.49C>T	p.Arg17Trp	missense	Exon 2 of 3	ENSP00000447161.1	O14508

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000287

AC:

AN:

173960

AF XY:

0.0000212

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000751

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000575

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000452

AC:

AN:

1417182

Hom.:

Cov.:

AF XY:

0.0000499

AC XY:

AN XY:

701318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32456

American (AMR)

AF:

0.00

AC:

AN:

38894

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25386

East Asian (EAS)

AF:

0.00

AC:

AN:

37216

South Asian (SAS)

AF:

0.00

AC:

AN:

81160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

1088774

Other (OTH)

AF:

0.00

AC:

AN:

58538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152002

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41396

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000676

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000254

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.42

Eigen

Benign

0.15

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.85

M_CAP

Benign

0.022

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

0.96

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

REVEL

Benign

0.072

Sift

Uncertain

0.015

Sift4G

Uncertain

0.015

Polyphen

0.99

Vest4

0.24

MutPred

0.31

Gain of loop (P = 0.024)

MVP

0.52

MPC

0.65

ClinPred

0.26

GERP RS

4.4

PromoterAI

0.035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.078

gMVP

0.48

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over