Genetic Variant STAM2:p.Met392Val (chr2-152126231-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

6 publications found

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:

ENSG00000304591 (HGNC:):

ENSG00000304591 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2651438.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005843.6. 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
	STAM2	NM_005843.6	MANE Select	c.1174A>G	p.Met392Val	missense	Exon 12 of 14	NP_005834.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STAM2	ENST00000263904.5	TSL:1 MANE Select	c.1174A>G	p.Met392Val	missense	Exon 12 of 14	ENSP00000263904.4	O75886-1
STAM2	ENST00000482997.5	TSL:1	n.1261A>G		non_coding_transcript_exon	Exon 12 of 12
STAM2	ENST00000865052.1		c.1228A>G	p.Met410Val	missense	Exon 13 of 15	ENSP00000535111.1

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

GnomAD2 exomes

AF:

0.00350

AC:

812

AN:

231802

AF XY:

0.00324

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 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

African (AFR)

AF:

0.000373

AC:

AN:

32148

American (AMR)

AF:

0.000401

AC:

AN:

39924

Ashkenazi Jewish (ASJ)

AF:

0.00662

AC:

167

AN:

25238

East Asian (EAS)

AF:

0.0000261

AC:

AN:

38360

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80494

European-Finnish (FIN)

AF:

0.0141

AC:

745

AN:

52658

Middle Eastern (MID)

AF:

0.000885

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.00214

AC:

2356

AN:

1099896

Other (OTH)

AF:

0.00222

AC:

131

AN:

58994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

164

327

491

654

818

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.00341

AC:

520

AN:

152330

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

271

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41582

American (AMR)

AF:

0.000523

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0132

AC:

140

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00498

AC:

339

AN:

68036

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

118

148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00367

Hom.:

Bravo

AF:

0.00187

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00328

AC:

398

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.3

(source)

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

PhyloP100

-0.26

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

Mutation Taster

=93/7

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