8-73688713-T-G

Variant summary

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

The NM_001164380.2(STAU2):c.215A>C(p.Glu72Ala) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAU2 NM_001164380.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67

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.215A>C	p.Glu72Ala	missense_variant	5/15	ENST00000524300.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAU2	ENST00000524300.6	c.215A>C	p.Glu72Ala	missense_variant	5/15	2	NM_001164380.2	P1
	ENST00000533978.1	n.143+13141T>G		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: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2024

The c.215A>C (p.E72A) alteration is located in exon 5 (coding exon 2) of the STAU2 gene. This alteration results from a A to C substitution at nucleotide position 215, causing the glutamic acid (E) at amino acid position 72 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	0.16
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
Cadd	Pathogenic	28
Dann	Uncertain	0.99
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;.;D;D;D;D;D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.47	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.68	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.23	T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.43	T;T;T;T;T;T;T;T;T;T;.
Polyphen		1.0, 0.91, 1.0	.;.;.;D;P;.;.;.;.;D;.
Vest4		0.43
MutPred		0.19		Gain of MoRF binding (P = 0.0244);.;Gain of MoRF binding (P = 0.0244);.;.;Gain of MoRF binding (P = 0.0244);.;Gain of MoRF binding (P = 0.0244);Gain of MoRF binding (P = 0.0244);.;Gain of MoRF binding (P = 0.0244);
MVP		0.15
MPC		0.55
ClinPred		0.92	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-74600948;