Genetic Variant STAP2:p.Thr282Ile (chr19-4325530-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001013841.2(STAP2):c.845C>T(p.Thr282Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000548 in 1,597,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 0 hom. )

Consequence

STAP2
NM_001013841.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0120

Variant links:

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]

STAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027056813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAP2	NM_001013841.2 link	c.845C>T	p.Thr282Ile	missense_variant	Exon 10 of 13	ENST00000594605.6	NP_001013863.1	Q9UGK3-1
STAP2	NM_017720.3 link	c.845C>T	p.Thr282Ile	missense_variant	Exon 10 of 13		NP_060190.2	Q9UGK3-2
STAP2	XM_011528123.2 link	c.845C>T	p.Thr282Ile	missense_variant	Exon 10 of 13		XP_011526425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAP2	ENST00000594605.6 link	c.845C>T	p.Thr282Ile	missense_variant	Exon 10 of 13	1	NM_001013841.2	ENSP00000471052.1		Q9UGK3-1

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000339

AC:

AN:

232828

Hom.:

AF XY:

0.000257

AC XY:

AN XY:

124646

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.0000598

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000672

Gnomad OTH exome

AF:

0.000880

GnomAD4 exome

AF:

0.000572

AC:

827

AN:

1444846

Hom.:

Cov.:

AF XY:

0.000509

AC XY:

365

AN XY:

717358

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.0000686

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.000195

Gnomad4 NFE exome

AF:

0.000714

Gnomad4 OTH exome

AF:

0.000351

GnomAD4 genome

AF:

0.000315

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000447

Hom.:

Bravo

AF:

0.000366

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000396

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.845C>T (p.T282I) alteration is located in exon 10 (coding exon 10) of the STAP2 gene. This alteration results from a C to T substitution at nucleotide position 845, causing the threonine (T) at amino acid position 282 to be replaced by an isoleucine (I). 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

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.12

.;T;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.58

T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.027

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;.

PrimateAI

Uncertain

0.54

Sift4G

Uncertain

0.043

D;T;.

Polyphen

0.25

B;B;.

Vest4

0.087

MVP

0.30

MPC

0.55

ClinPred

0.016

GERP RS

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.062

gMVP

0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over