2-152120770-T-G

Variant names:

• chr2-152120770-T-G
• rs140582341
• NM_005843.6:c.1382A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005843.6(STAM2):​c.1382A>C​(p.Tyr461Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y461C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAM2 NM_005843.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.99
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37191722).

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.1382A>C	p.Tyr461Ser	missense	Exon 14 of 14	NP_005834.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAM2	ENST00000263904.5	TSL:1 MANE Select	c.1382A>C	p.Tyr461Ser	missense	Exon 14 of 14	ENSP00000263904.4	O75886-1
	STAM2	ENST00000865052.1		c.1436A>C	p.Tyr479Ser	missense	Exon 15 of 15	ENSP00000535111.1
	STAM2	ENST00000968933.1		c.1337A>C	p.Tyr446Ser	missense	Exon 14 of 14	ENSP00000638992.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.042
Eigen_PC	Benign	0.080
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.16	T
Polyphen		0.23	B
Vest4		0.57
MutPred		0.25		Loss of phosphorylation at Y461 (P = 0.0459)
MVP		0.48
MPC		0.32
ClinPred		0.83	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs140582341; hg19: chr2-152977284;