8-73422626-C-T

Variant names:

• chr8-73422626-C-T
• rs527332052
• NM_001164380.2:c.1607G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001164380.2(STAU2):​c.1607G>A​(p.Gly536Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000022 in 1,363,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G536V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: STAU2 NM_001164380.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77
• Publications: 0 publications found

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]

STAU2-AS1 (HGNC:44101): (STAU2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27652812).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164380.2. 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
	STAU2	NM_001164380.2	MANE Select	c.1607G>A	p.Gly536Asp	missense	Exon 14 of 15	NP_001157852.1	Q9NUL3-1
	STAU2	NM_001164381.2		c.1511G>A	p.Gly504Asp	missense	Exon 13 of 14	NP_001157853.1	Q9NUL3-2
	STAU2	NM_001164382.2		c.1409G>A	p.Gly470Asp	missense	Exon 13 of 14	NP_001157854.1	Q9NUL3-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAU2	ENST00000524300.6	TSL:2 MANE Select	c.1607G>A	p.Gly536Asp	missense	Exon 14 of 15	ENSP00000428756.1	Q9NUL3-1
	STAU2	ENST00000522695.5	TSL:1	c.1511G>A	p.Gly504Asp	missense	Exon 11 of 12	ENSP00000428456.1	Q9NUL3-2
	STAU2	ENST00000946925.1		c.1613G>A	p.Gly538Asp	missense	Exon 13 of 14	ENSP00000616984.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000220 AC: 3 AN: 1363060 Hom.: 0 Cov.: 29 AF XY: 0.00000149 AC XY: 1 AN XY: 671410

African (AFR) AF: 0.00 AC: 0 AN: 30320

American (AMR) AF: 0.00 AC: 0 AN: 30330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24864

East Asian (EAS) AF: 0.00 AC: 0 AN: 34626

South Asian (SAS) AF: 0.00 AC: 0 AN: 73678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1071658

Other (OTH) AF: 0.0000175 AC: 1 AN: 57094

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.8
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.086	T
Vest4		0.58
MutPred		0.30		Loss of methylation at K503 (P = 0.0786)
MVP		0.30
MPC		0.44
ClinPred		0.85	D
GERP RS		3.5
Varity_R		0.18
gMVP		0.30
Mutation Taster		=74/26	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: rs527332052; hg19: chr8-74334861;