Genetic Variant SOCS2:n.970A>G (chr12-93583178-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XR_944810.2(SOCS2):n.970A>G variant causes a non coding transcript exon 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
XR_944810.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0760

Publications

36 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: Benign. The variant received -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	Effect	Exon rank	Protein
SOCS2	XR_944810.2 link	n.970A>G	non_coding_transcript_exon_variant	Exon 3 of 4
SOCS2	XM_011538936.2 link	c.*132A>G	3_prime_UTR_variant	Exon 3 of 3	XP_011537238.1
SOCS2	XM_011538929.2 link	c.592-2510A>G	intron_variant	Intron 2 of 2	XP_011537231.1
SOCS2	XM_011538935.2 link	c.591+8005A>G	intron_variant	Intron 2 of 2	XP_011537237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOCS2	ENST00000549510.1 link	c.*132A>G		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000474888.1		S4R3Z4

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34196

AN:

151734

Hom.:

3902

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.225

AC:

34212

AN:

151850

Hom.:

3906

Cov.:

AF XY:

0.223

AC XY:

16528

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.234

AC:

9700

AN:

41386

American (AMR)

AF:

0.242

AC:

3689

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

439

AN:

3468

East Asian (EAS)

AF:

0.305

AC:

1566

AN:

5136

South Asian (SAS)

AF:

0.138

AC:

663

AN:

4804

European-Finnish (FIN)

AF:

0.234

AC:

2459

AN:

10522

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.222

AC:

15097

AN:

67950

Other (OTH)

AF:

0.199

AC:

419

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1308

2616

3925

5233

6541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<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:

0.220

Hom.:

17118

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

(source)

DANN

Benign

0.87

PhyloP100

-0.076

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over