chr12-130808702-T-C

Position:

• chr12-130808702-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001351052.2(STX2):​c.-105A>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00212 in 1,610,222 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (40 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (29 hom.)
• Consequence: STX2 NM_001351052.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.83

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006135136).
• BP6: Variant 12-130808702-T-C is Benign according to our data. Variant chr12-130808702-T-C is described in ClinVar as [Benign]. Clinvar id is 714325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1735/152354) while in subpopulation AFR AF= 0.0397 (1651/41580). AF 95% confidence interval is 0.0381. There are 40 homozygotes in gnomad4. There are 817 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 40 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX2	NM_194356.4	c.283A>G	p.Ile95Val	missense_variant, splice_region_variant	5/11	ENST00000392373.7	NP_919337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX2	ENST00000392373.7	c.283A>G	p.Ile95Val	missense_variant, splice_region_variant	5/11	5	NM_194356.4	ENSP00000376178.2

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1720 AN: 152236 Hom.: 39 Cov.: 33

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00303 AC: 750 AN: 247352 Hom.: 20 AF XY: 0.00233 AC XY: 311 AN XY: 133450

Gnomad AFR exome AF: 0.0413

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000687

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00115 AC: 1671 AN: 1457868 Hom.: 29 Cov.: 30 AF XY: 0.00100 AC XY: 725 AN XY: 725002

Gnomad4 AFR exome AF: 0.0390

Gnomad4 AMR exome AF: 0.00211

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000353

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000928

Gnomad4 OTH exome AF: 0.00267

GnomAD4 genome AF: 0.0114 AC: 1735 AN: 152354 Hom.: 40 Cov.: 33 AF XY: 0.0110 AC XY: 817 AN XY: 74506

Gnomad4 AFR AF: 0.0397

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00312 Hom.: 4

Bravo AF: 0.0124

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0390 AC: 172

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00370 AC: 449

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D
MetaRNN	Benign	0.0061	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.69	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.55	P;P
Vest4		0.47
MVP		0.80
MPC		0.13
ClinPred		0.049	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.59
gMVP		0.18

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

LitVar

Other links and lift over

dbSNP: rs76596600; hg19: chr12-131293247;