8-73688702-G-A

Variant summary

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

The NM_001164380.2(STAU2):c.226C>T(p.Pro76Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAU2 NM_001164380.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.55

Genes affected

STAU2 (HGNC:11371): (staufen double-stranded RNA binding protein 2) Staufen homolog 2 is a member of the family of double-stranded RNA (dsRNA)-binding proteins involved in the transport and/or localization of mRNAs to different subcellular compartments and/or organelles. These proteins are characterized by the presence of multiple dsRNA-binding domains which are required to bind RNAs having double-stranded secondary structures. Staufen homolog 2 shares 48.5% and 59.9% similarity with drosophila and human staufen, respectively. The exact function of Staufen homolog 2 is not known, but since it contains 3 copies of conserved dsRNA binding domain, it could be involved in double-stranded RNA binding events. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

(HGNC:):

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/exons	MANE	UniProt
STAU2	NM_001164380.2	c.226C>T	p.Pro76Ser	missense_variant	5/15	ENST00000524300.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAU2	ENST00000524300.6	c.226C>T	p.Pro76Ser	missense_variant	5/15	2	NM_001164380.2	P1
	ENST00000533978.1	n.143+13130G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
Cadd	Pathogenic	29
Dann	Pathogenic	1.0
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;.;D;D;D;D;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.54	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0070	D;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.039	D;T;D;T;D;D;D;T;T;T;.
Polyphen		1.0	.;.;.;D;D;.;.;.;.;D;.
Vest4		0.60
MutPred		0.28		Gain of phosphorylation at P44 (P = 0.0567);.;Gain of phosphorylation at P44 (P = 0.0567);.;.;Gain of phosphorylation at P44 (P = 0.0567);.;Gain of phosphorylation at P44 (P = 0.0567);Gain of phosphorylation at P44 (P = 0.0567);.;Gain of phosphorylation at P44 (P = 0.0567);
MVP		0.23
MPC		0.93
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.30
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-74600937; COSMIC: COSV62477253; COSMIC: COSV62477253;