2-152135550-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_005843.6(STAM2):​c.758C>G​(p.Ser253Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

STAM2
NM_005843.6 missense

Scores

8
8
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.36
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.945

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STAM2NM_005843.6 linkc.758C>G p.Ser253Cys missense_variant Exon 8 of 14 ENST00000263904.5 NP_005834.4 O75886-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STAM2ENST00000263904.5 linkc.758C>G p.Ser253Cys missense_variant Exon 8 of 14 1 NM_005843.6 ENSP00000263904.4 O75886-1
STAM2ENST00000463854.5 linkn.865C>G non_coding_transcript_exon_variant Exon 8 of 11 1
STAM2ENST00000482997.5 linkn.845C>G non_coding_transcript_exon_variant Exon 8 of 12 1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
29
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.25
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.34
T
Eigen
Pathogenic
0.93
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.95
D
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Uncertain
2.7
M
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-4.4
D
REVEL
Pathogenic
0.68
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.80
MutPred
0.86
Gain of catalytic residue at P252 (P = 0.0122);
MVP
0.90
MPC
0.30
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.79
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs767812065; hg19: chr2-152992064; API