chr12-130827218-T-C

Position:

• chr12-130827218-T-C

Variant summary

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

The NM_194356.4(STX2):​c.80A>G​(p.His27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: STX2 NM_194356.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45

Genes affected

STX2 (HGNC:3403): (syntaxin 2) The product of this gene belongs to the syntaxin/epimorphin family of proteins. The syntaxins are a large protein family implicated in the targeting and fusion of intracellular transport vesicles. The product of this gene regulates epithelial-mesenchymal interactions and epithelial cell morphogenesis and activation. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

STX2 (HGNC:):

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=0.14015624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX2	NM_194356.4	c.80A>G	p.His27Arg	missense_variant	2/11	ENST00000392373.7	NP_919337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX2	ENST00000392373.7	c.80A>G	p.His27Arg	missense_variant	2/11	5	NM_194356.4	ENSP00000376178.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

Oct 02, 2023

The c.80A>G (p.H27R) alteration is located in exon 2 (coding exon 2) of the STX2 gene. This alteration results from a A to G substitution at nucleotide position 80, causing the histidine (H) at amino acid position 27 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	0.073
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.37
DEOGEN2	Benign	0.078	.;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.062
Sift	Benign	0.49	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.33	B;B
Vest4		0.24
MutPred		0.37		Gain of catalytic residue at E24 (P = 5e-04);Gain of catalytic residue at E24 (P = 5e-04);
MVP		0.45
MPC		0.26
ClinPred		0.73	D
GERP RS		4.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.10
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1593182326; hg19: chr12-131311763;