19-4324572-C-A

Variant names:

• chr19-4324572-C-A
• NM_001013841.2:c.1073-43G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017720.3(STAP2):​c.1168G>T​(p.Gly390Cys) 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. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAP2 NM_017720.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.902

Genes affected

STAP2 (HGNC:30430): (signal transducing adaptor family member 2) This gene encodes the substrate of breast tumor kinase, an Src-type non-receptor tyrosine kinase. The encoded protein possesses domains and several tyrosine phosphorylation sites characteristic of adaptor proteins that mediate the interactions linking proteins involved in signal transduction pathways. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092035234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAP2	NM_001013841.2	c.1073-43G>T		intron_variant	Intron 11 of 12	ENST00000594605.6	NP_001013863.1
STAP2	NM_017720.3	c.1168G>T	p.Gly390Cys	missense_variant	Exon 12 of 13		NP_060190.2
STAP2	XM_011528123.2	c.1165G>T	p.Gly389Cys	missense_variant	Exon 12 of 13		XP_011526425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAP2	ENST00000594605.6	c.1073-43G>T		intron_variant	Intron 11 of 12	1	NM_001013841.2	ENSP00000471052.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1168G>T (p.G390C) alteration is located in exon 12 (coding exon 12) of the STAP2 gene. This alteration results from a G to T substitution at nucleotide position 1168, causing the glycine (G) at amino acid position 390 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.67
DANN	Benign	0.72
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.37	T
Sift4G	Pathogenic	0.0010	D
Polyphen		0.49	P
Vest4		0.18
MutPred		0.55		Loss of disorder (P = 0.0232);
MVP		0.072
MPC		0.63
ClinPred		0.16	T
GERP RS		-0.77
gMVP		0.11

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-4324569;