12-130829669-T-C

Variant names:

• chr12-130829669-T-C
• rs4334059
• NM_194356.4:c.31-2402A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194356.4(STX2):​c.31-2402A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,154 control chromosomes in the GnomAD database, including 30,294 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (30294 hom., cov: 33)
• Consequence: STX2 NM_194356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX2	NM_194356.4	c.31-2402A>G		intron_variant	Intron 1 of 10	ENST00000392373.7	NP_919337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX2	ENST00000392373.7	c.31-2402A>G		intron_variant	Intron 1 of 10	5	NM_194356.4	ENSP00000376178.2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94745 AN: 152036 Hom.: 30281 Cov.: 33

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.623 AC: 94792 AN: 152154 Hom.: 30294 Cov.: 33 AF XY: 0.628 AC XY: 46739 AN XY: 74392

African (AFR) AF: 0.492 AC: 20416 AN: 41500

American (AMR) AF: 0.636 AC: 9731 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2065 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4569 AN: 5172

South Asian (SAS) AF: 0.762 AC: 3681 AN: 4832

European-Finnish (FIN) AF: 0.696 AC: 7378 AN: 10596

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.662 AC: 44970 AN: 67974

Other (OTH) AF: 0.619 AC: 1308 AN: 2114

Alfa AF: 0.639 Hom.: 14369

Bravo AF: 0.612

Asia WGS AF: 0.795 AC: 2768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.59
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs4334059; hg19: chr12-131314214;