chr8-73582796-G-C

Position:

• chr8-73582796-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164380.2(STAU2):​c.1196C>G​(p.Pro399Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STAU2 NM_001164380.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.16

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07098913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAU2	NM_001164380.2	c.1196C>G	p.Pro399Arg	missense_variant	12/15	ENST00000524300.6	NP_001157852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAU2	ENST00000524300.6	c.1196C>G	p.Pro399Arg	missense_variant	12/15	2	NM_001164380.2	ENSP00000428756.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460004 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726400

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: 0.0000116

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2024

The c.1196C>G (p.P399R) alteration is located in exon 12 (coding exon 9) of the STAU2 gene. This alteration results from a C to G substitution at nucleotide position 1196, causing the proline (P) at amino acid position 399 to be replaced by an arginine (R). 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	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	26
DANN	Benign	0.82
DEOGEN2	Benign	0.0095	.;T;.;.;.;.;.;T;.;.;.;.;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.054
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;.;D;D;D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.071	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	.;L;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.36	N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.038	D;D;D;T;T;T;T;T;T;T;T;T;D
Sift4G	Benign	0.55	T;T;D;T;T;T;T;T;T;T;T;D;T
Polyphen		0.0040, 0.054	.;.;.;.;.;.;B;B;.;.;.;.;.
Vest4		0.15
MutPred		0.23		Gain of solvent accessibility (P = 0.1045);.;.;.;.;Gain of solvent accessibility (P = 0.1045);.;.;.;Gain of solvent accessibility (P = 0.1045);.;.;.;
MVP		0.068
MPC		0.29
ClinPred		0.28	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.071
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr8-74495031;