rs886037633

Variant names:

• chr2-73847420-GC-G
• rs886037633
• NM_213622.4:c.411delC

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_213622.4(STAMBP):​c.411delC​(p.Ile138SerfsTer12) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAMBP NM_213622.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.28
• 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000286244 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-73847420-GC-G is Pathogenic according to our data. Variant chr2-73847420-GC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 50797.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213622.4. 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
	STAMBP	NM_213622.4	MANE Select	c.411delC	p.Ile138SerfsTer12	frameshift	Exon 5 of 10	NP_998787.1	O95630-1
	STAMBP	NM_001353967.2		c.411delC	p.Ile138SerfsTer12	frameshift	Exon 6 of 11	NP_001340896.1	A0A140VK54
	STAMBP	NM_001353968.2		c.411delC	p.Ile138SerfsTer12	frameshift	Exon 5 of 10	NP_001340897.1	A0A140VK54

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAMBP	ENST00000394070.7	TSL:1 MANE Select	c.411delC	p.Ile138SerfsTer12	frameshift	Exon 5 of 10	ENSP00000377633.2	O95630-1
	STAMBP	ENST00000394073.6	TSL:1	c.411delC	p.Ile138SerfsTer12	frameshift	Exon 6 of 11	ENSP00000377636.1	O95630-1
	STAMBP	ENST00000683877.1		c.411delC	p.Ile138SerfsTer12	frameshift	Exon 6 of 11	ENSP00000507446.1	A0A804HJC8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Microcephaly-capillary malformation syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3
Mutation Taster		=0/200	disease causing (ClinVar)

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: rs886037633; hg19: chr2-74074547;