Genetic Variant SOCS2:p.Ala26Glu (chr12-93572974-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001270471.2(SOCS2):c.77C>A(p.Ala26Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A26V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SOCS2
NM_001270471.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.275

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06535718).

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.77C>A	p.Ala26Glu	missense	Exon 1 of 2	NP_001257400.1	O14508
SOCS2	NM_001270467.2		c.77C>A	p.Ala26Glu	missense	Exon 2 of 3	NP_001257396.1	O14508
SOCS2	NM_001270468.2		c.77C>A	p.Ala26Glu	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.77C>A	p.Ala26Glu	missense	Exon 1 of 2	ENSP00000449227.1	O14508
SOCS2	ENST00000340600.6	TSL:1	c.77C>A	p.Ala26Glu	missense	Exon 2 of 3	ENSP00000339428.2	O14508
SOCS2	ENST00000549122.5	TSL:1	c.77C>A	p.Ala26Glu	missense	Exon 2 of 3	ENSP00000447161.1	O14508

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1415762

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700432

African (AFR)

AF:

0.00

AC:

AN:

32458

American (AMR)

AF:

0.00

AC:

AN:

38474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25366

East Asian (EAS)

AF:

0.00

AC:

AN:

37182

South Asian (SAS)

AF:

0.00

AC:

AN:

80920

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089152

Other (OTH)

AF:

0.00

AC:

AN:

58632

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.26

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.45

M_CAP

Benign

0.012

MetaRNN

Benign

0.065

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

PhyloP100

0.28

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.58

REVEL

Benign

0.041

Sift

Benign

0.35

Sift4G

Benign

0.88

Polyphen

0.020

Vest4

0.24

MutPred

0.20

Loss of glycosylation at S25 (P = 0.1365)

MVP

0.26

MPC

0.70

ClinPred

0.11

GERP RS

3.1

PromoterAI

0.096

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.053

gMVP

0.72

Mutation Taster

=89/11

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over