Genetic Variant STAP2:p.Pro274Ala (chr19-4326951-G-C) – 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.820C>G(p.Pro274Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000069 in 1,551,562 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

STAP2
NM_001013841.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.737

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=0.061809003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAP2	NM_001013841.2 link	c.820C>G	p.Pro274Ala	missense_variant	Exon 9 of 13	ENST00000594605.6	NP_001013863.1	Q9UGK3-1
STAP2	NM_017720.3 link	c.820C>G	p.Pro274Ala	missense_variant	Exon 9 of 13		NP_060190.2	Q9UGK3-2
STAP2	XM_011528123.2 link	c.820C>G	p.Pro274Ala	missense_variant	Exon 9 of 13		XP_011526425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAP2	ENST00000594605.6 link	c.820C>G	p.Pro274Ala	missense_variant	Exon 9 of 13	1	NM_001013841.2	ENSP00000471052.1		Q9UGK3-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000449

AC:

AN:

155944

Hom.:

AF XY:

0.0000243

AC XY:

AN XY:

82162

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000885

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000166

Gnomad OTH exome

AF:

0.000454

GnomAD4 exome

AF:

0.0000722

AC:

101

AN:

1399238

Hom.:

Cov.:

AF XY:

0.0000609

AC XY:

AN XY:

690212

show subpopulations

Gnomad4 AFR exome

AF:

0.000570

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000621

Gnomad4 OTH exome

AF:

0.000172

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000121

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.820C>G (p.P274A) alteration is located in exon 9 (coding exon 9) of the STAP2 gene. This alteration results from a C to G substitution at nucleotide position 820, causing the proline (P) at amino acid position 274 to be replaced by an alanine (A). 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

0.065

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.18

.;T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.48

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.062

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

L;L;.

PrimateAI

Benign

0.39

Sift4G

Uncertain

0.055

T;T;.

Polyphen

0.0080

B;B;.

Vest4

0.14

MVP

0.41

MPC

0.34

ClinPred

0.023

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.20

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

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