Genetic Variant STAP2:p.Pro359Ser (chr19-4324527-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.1075C>T(p.Pro359Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,567,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

STAP2
NM_001013841.2 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

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=0.007417202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAP2	NM_001013841.2 link	c.1075C>T	p.Pro359Ser	missense_variant, splice_region_variant	Exon 12 of 13	ENST00000594605.6	NP_001013863.1	Q9UGK3-1
STAP2	NM_017720.3 link	c.1213C>T	p.Pro405Ser	missense_variant	Exon 12 of 13		NP_060190.2	Q9UGK3-2
STAP2	XM_011528123.2 link	c.1210C>T	p.Pro404Ser	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 link	c.1075C>T	p.Pro359Ser	missense_variant, splice_region_variant	Exon 12 of 13	1	NM_001013841.2	ENSP00000471052.1		Q9UGK3-1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000212

AC:

AN:

174210

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

92570

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.0000370

Gnomad ASJ exome

AF:

0.000228

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000860

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.000211

GnomAD4 exome

AF:

0.000117

AC:

166

AN:

1414660

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

699164

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.0000261

Gnomad4 ASJ exome

AF:

0.000118

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000722

Gnomad4 NFE exome

AF:

0.000110

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

AF:

0.000197

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000196

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.000234

AC:

ExAC

AF:

0.000129

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1213C>T (p.P405S) alteration is located in exon 12 (coding exon 12) of the STAP2 gene. This alteration results from a C to T substitution at nucleotide position 1213, causing the proline (P) at amino acid position 405 to be replaced by a serine (S). 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

0.096

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.17

.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.0072

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

.;L

PrimateAI

Benign

0.29

Sift4G

Uncertain

0.026

D;T

Polyphen

0.78

P;B

Vest4

0.20

MVP

0.37

MPC

0.35

ClinPred

0.048

GERP RS

2.7

Varity_R

0.034

gMVP

0.28

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