chr2-73862254-C-G

Variant names:

• chr2-73862254-C-G
• rs397509390
• NM_213622.4:c.1270C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_213622.4(STAMBP):​c.1270C>G​(p.Arg424Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R424P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAMBP NM_213622.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.02
• Publications: 1 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAMBP	NM_213622.4	c.1270C>G	p.Arg424Gly	missense_variant	Exon 10 of 10	ENST00000394070.7	NP_998787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAMBP	ENST00000394070.7	c.1270C>G	p.Arg424Gly	missense_variant	Exon 10 of 10	1	NM_213622.4	ENSP00000377633.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D;D;D;D
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.80	.;T;.;.
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	3.0	M;M;M;M
PhyloP100		5.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.6	D;D;D;D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.52
MutPred		0.43		Loss of solvent accessibility (P = 0.0044);Loss of solvent accessibility (P = 0.0044);Loss of solvent accessibility (P = 0.0044);Loss of solvent accessibility (P = 0.0044);
MVP		0.73
MPC		1.2
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.90
gMVP		0.86
Mutation Taster		=33/67	disease causing

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

Other links and lift over

dbSNP: rs397509390; hg19: chr2-74089381;