19-4327007-C-G

Variant names:

• chr19-4327007-C-G
• rs1199931190
• NM_001013841.2:c.764G>C

Variant summary

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

The NM_001013841.2(STAP2):​c.764G>C​(p.Gly255Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: STAP2 NM_001013841.2 missense, splice_region
• Scores: Splicing: ADA: 0.9996
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAP2	NM_001013841.2	c.764G>C	p.Gly255Ala	missense_variant, splice_region_variant	Exon 9 of 13	ENST00000594605.6	NP_001013863.1
STAP2	NM_017720.3	c.764G>C	p.Gly255Ala	missense_variant, splice_region_variant	Exon 9 of 13		NP_060190.2
STAP2	XM_011528123.2	c.764G>C	p.Gly255Ala	missense_variant, splice_region_variant	Exon 9 of 13		XP_011526425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAP2	ENST00000594605.6	c.764G>C	p.Gly255Ala	missense_variant, splice_region_variant	Exon 9 of 13	1	NM_001013841.2	ENSP00000471052.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000570 AC: 1 AN: 175554 Hom.: 0 AF XY: 0.0000106 AC XY: 1 AN XY: 94028

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: 0.0000394

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412210 Hom.: 0 Cov.: 34 AF XY: 0.00000143 AC XY: 1 AN XY: 698424

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.764G>C (p.G255A) alteration is located in exon 9 (coding exon 9) of the STAP2 gene. This alteration results from a G to C substitution at nucleotide position 764, causing the glycine (G) at amino acid position 255 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	0.27
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.45
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	1.8	L;L;.
PrimateAI	Uncertain	0.57	T
Sift4G	Benign	0.20	T;T;.
Polyphen		0.99	D;D;.
Vest4		0.46
MutPred		0.37		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);.;
MVP		0.65
MPC		0.44
ClinPred		0.55	D
GERP RS		5.1
Varity_R		0.15
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.98
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs1199931190; hg19: chr19-4327004;