chr2-73847660-C-G

Variant names:

• chr2-73847660-C-G
• rs1553382055
• NM_213622.4:c.649C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_213622.4(STAMBP):​c.649C>G​(p.Gln217Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAMBP NM_213622.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• Publications: 0 publications found

Genes affected

STAMBP (HGNC:16950): (STAM binding protein) Cytokine-mediated signal transduction in the JAK-STAT cascade requires the involvement of adaptor molecules. One such signal-transducing adaptor molecule contains an SH3 domain that is required for induction of MYC and cell growth. The protein encoded by this gene binds to the SH3 domain of the signal-transducing adaptor molecule, and plays a critical role in cytokine-mediated signaling for MYC induction and cell cycle progression. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]

STAMBP Gene-Disease associations (from GenCC):

• microcephaly-capillary malformation syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ENSG00000286244 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053964138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAMBP	NM_213622.4	c.649C>G	p.Gln217Glu	missense_variant	Exon 5 of 10	ENST00000394070.7	NP_998787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAMBP	ENST00000394070.7	c.649C>G	p.Gln217Glu	missense_variant	Exon 5 of 10	1	NM_213622.4	ENSP00000377633.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	19
DANN	Benign	0.39
DEOGEN2	Benign	0.082	T;T;.;T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.39	.;T;T;.;.
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.054	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L;L;.;L;L
PhyloP100		2.3
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.65	N;N;N;N;N
REVEL	Benign	0.028
Sift	Benign	0.76	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	B;B;.;B;B
Vest4		0.12
MutPred		0.20		Gain of glycosylation at S215 (P = 0.0841);Gain of glycosylation at S215 (P = 0.0841);Gain of glycosylation at S215 (P = 0.0841);Gain of glycosylation at S215 (P = 0.0841);Gain of glycosylation at S215 (P = 0.0841);
MVP		0.38
MPC		0.32
ClinPred		0.032	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.027
gMVP		0.26
Mutation Taster		=87/13	polymorphism

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: rs1553382055; hg19: chr2-74074787;