chr2-152120770-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005843.6(STAM2):ā€‹c.1382A>Gā€‹(p.Tyr461Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000255 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00018 ( 0 hom., cov: 32)
Exomes š‘“: 0.00026 ( 0 hom. )

Consequence

STAM2
NM_005843.6 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.99
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
STAM2NM_005843.6 linkuse as main transcriptc.1382A>G p.Tyr461Cys missense_variant 14/14 ENST00000263904.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
STAM2ENST00000263904.5 linkuse as main transcriptc.1382A>G p.Tyr461Cys missense_variant 14/141 NM_005843.6 P1O75886-1
STAM2ENST00000489389.1 linkuse as main transcriptn.954A>G non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.000177
AC:
27
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.000367
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000143
AC:
36
AN:
251384
Hom.:
0
AF XY:
0.000140
AC XY:
19
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.000290
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000263
AC:
384
AN:
1461876
Hom.:
0
Cov.:
31
AF XY:
0.000246
AC XY:
179
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000131
Gnomad4 NFE exome
AF:
0.000329
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000177
AC:
27
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000367
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000295
Hom.:
1
Bravo
AF:
0.000178
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000107
AC:
13
EpiCase
AF:
0.000273
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 30, 2022The c.1382A>G (p.Y461C) alteration is located in exon 14 (coding exon 14) of the STAM2 gene. This alteration results from a A to G substitution at nucleotide position 1382, causing the tyrosine (Y) at amino acid position 461 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.014
T
MetaRNN
Uncertain
0.61
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.5
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-3.4
D
REVEL
Benign
0.17
Sift
Uncertain
0.0010
D
Sift4G
Benign
0.096
T
Polyphen
1.0
D
Vest4
0.68
MVP
0.68
MPC
0.32
ClinPred
0.33
T
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.24
gMVP
0.54

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.

Other links and lift over

dbSNP: rs140582341; hg19: chr2-152977284; COSMIC: COSV55730614; API