Variant 2-152126231-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005843.6(STAM2):c.1174A>G(p.Met392Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,585,692 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 25 hom. )

Consequence

STAM2
NM_005843.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.256

Variant links:

Genes affected

STAM2 (HGNC:11358): (signal transducing adaptor molecule 2) The protein encoded by this gene is closely related to STAM, an adaptor protein involved in the downstream signaling of cytokine receptors, both of which contain a SH3 domain and the immunoreceptor tyrosine-based activation motif (ITAM). Similar to STAM, this protein acts downstream of JAK kinases, and is phosphorylated in response to cytokine stimulation. This protein and STAM thus are thought to exhibit compensatory effects on the signaling pathway downstream of JAK kinases upon cytokine stimulation. [provided by RefSeq, Jul 2008]

STAM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031575859).

BP6

Variant 2-152126231-T-C is Benign according to our data. Variant chr2-152126231-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2651438.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAM2	NM_005843.6 linkuse as main transcript	c.1174A>G	p.Met392Val	missense_variant	12/14	ENST00000263904.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAM2	ENST00000263904.5 linkuse as main transcript	c.1174A>G	p.Met392Val	missense_variant	12/14	1	NM_005843.6	P1	O75886-1
STAM2	ENST00000482997.5 linkuse as main transcript	n.1261A>G		non_coding_transcript_exon_variant	12/12	1

Frequencies

GnomAD3 genomes

AF:

0.00342

AC:

520

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00498

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00350

AC:

812

AN:

231802

Hom.:

AF XY:

0.00324

AC XY:

407

AN XY:

125766

show subpopulations

Gnomad AFR exome

AF:

0.000198

Gnomad AMR exome

AF:

0.000337

Gnomad ASJ exome

AF:

0.00628

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000373

Gnomad FIN exome

AF:

0.0140

Gnomad NFE exome

AF:

0.00378

Gnomad OTH exome

AF:

0.00611

GnomAD4 exome

AF:

0.00240

AC:

3434

AN:

1433362

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

1796

AN XY:

712808

show subpopulations

Gnomad4 AFR exome

AF:

0.000373

Gnomad4 AMR exome

AF:

0.000401

Gnomad4 ASJ exome

AF:

0.00662

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.0141

Gnomad4 NFE exome

AF:

0.00214

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00341

AC:

520

AN:

152330

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

271

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.00498

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00389

Hom.:

Bravo

AF:

0.00187

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00328

AC:

398

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

STAM2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.3

DANN

Benign

0.60

DEOGEN2

Benign

0.065

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.82

MutationTaster

Benign

0.71

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.34

REVEL

Benign

0.062

Sift

Benign

0.72

Sift4G

Benign

0.55

Polyphen

0.0

Vest4

0.11

MVP

0.16

MPC

0.044

ClinPred

0.0011

GERP RS

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.027

gMVP

0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over