Genetic Variant STAP2:c.1073-100G>A (chr19-4324629-C-T) – 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_017720.3(STAP2):c.1111G>A(p.Glu371Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000429 in 1,236,130 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

STAP2
NM_017720.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.29

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=0.053706706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAP2	NM_001013841.2 link	c.1073-100G>A		intron_variant	Intron 11 of 12	ENST00000594605.6	NP_001013863.1	Q9UGK3-1
STAP2	NM_017720.3 link	c.1111G>A	p.Glu371Lys	missense_variant	Exon 12 of 13		NP_060190.2	Q9UGK3-2
STAP2	XM_011528123.2 link	c.1108G>A	p.Glu370Lys	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.1073-100G>A		intron_variant	Intron 11 of 12	1	NM_001013841.2	ENSP00000471052.1		Q9UGK3-1

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

151030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000147

AC:

AN:

136086

Hom.:

AF XY:

0.0000137

AC XY:

AN XY:

72736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000488

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000193

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000461

AC:

AN:

1084986

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

543210

show subpopulations

Gnomad4 AFR exome

AF:

0.0000788

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000450

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000410

Gnomad4 OTH exome

AF:

0.000107

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151144

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73836

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1111G>A (p.E371K) alteration is located in exon 12 (coding exon 12) of the STAP2 gene. This alteration results from a G to A substitution at nucleotide position 1111, causing the glutamic acid (E) at amino acid position 371 to be replaced by a lysine (K). 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

-0.43

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.40

DANN

Benign

0.43

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00064

LIST_S2

Benign

0.78

M_CAP

Benign

0.0024

MetaRNN

Benign

0.054

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.44

Sift4G

Benign

0.71

Polyphen

0.0

Vest4

0.13

MutPred

0.38

Gain of ubiquitination at E371 (P = 0.0045);

MVP

0.13

MPC

0.30

ClinPred

0.028

GERP RS

-0.77

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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