rs760821330

Variant names:

• chr19-4326945-G-A
• rs760821330
• NM_001013841.2:c.826C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013841.2(STAP2):​c.826C>T​(p.Pro276Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000322 in 1,551,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 0.0000014 (0 hom.)
• Consequence: STAP2 NM_001013841.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.845
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092155516).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013841.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAP2	NM_001013841.2	MANE Select	c.826C>T	p.Pro276Ser	missense	Exon 9 of 13	NP_001013863.1	Q9UGK3-1
	STAP2	NM_017720.3		c.826C>T	p.Pro276Ser	missense	Exon 9 of 13	NP_060190.2	Q9UGK3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAP2	ENST00000594605.6	TSL:1 MANE Select	c.826C>T	p.Pro276Ser	missense	Exon 9 of 13	ENSP00000471052.1	Q9UGK3-1
	STAP2	ENST00000970041.1		c.958C>T	p.Pro320Ser	missense	Exon 9 of 13	ENSP00000640100.1
	STAP2	ENST00000970043.1		c.826C>T	p.Pro276Ser	missense	Exon 9 of 13	ENSP00000640102.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000643 AC: 1 AN: 155592 AF XY: 0.00

Gnomad AFR exome AF: 0.000117

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399118 Hom.: 0 Cov.: 35 AF XY: 0.00000145 AC XY: 1 AN XY: 690132

African (AFR) AF: 0.0000317 AC: 1 AN: 31586

American (AMR) AF: 0.00 AC: 0 AN: 35710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078886

Other (OTH) AF: 0.00 AC: 0 AN: 57992

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000724 AC: 3 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0232839), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000129 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.84
PrimateAI	Benign	0.42	T
Sift4G	Benign	0.43	T
Polyphen		0.34	B
Vest4		0.17
MVP		0.43
MPC		0.52
ClinPred		0.033	T
GERP RS		2.7
PromoterAI		0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.061
gMVP		0.29
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs760821330; hg19: chr19-4326942;