chr12-130789849-A-T

Variant names:

• chr12-130789849-A-T
• rs1236
• NM_194356.4:c.*2174T>A

Variant summary

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

The NM_194356.4(STX2):​c.*2174T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,462 control chromosomes in the GnomAD database, including 19,744 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 0.47 (19692 hom., cov: 33)
  • Exomes 𝑓: 0.64 (52 hom.)
• Consequence: STX2 NM_194356.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• Publications: 17 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX2	NM_194356.4	c.*2174T>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000392373.7	NP_919337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX2	ENST00000392373.7	c.*2174T>A		3_prime_UTR_variant	Exon 11 of 11	5	NM_194356.4	ENSP00000376178.2

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70943 AN: 152068 Hom.: 19698 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.638 AC: 176 AN: 276 Hom.: 52 Cov.: 0 AF XY: 0.640 AC XY: 105 AN XY: 164

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.636 AC: 173 AN: 272

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.466 AC: 70933 AN: 152186 Hom.: 19692 Cov.: 33 AF XY: 0.476 AC XY: 35404 AN XY: 74412

African (AFR) AF: 0.159 AC: 6615 AN: 41548

American (AMR) AF: 0.541 AC: 8275 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1662 AN: 3470

East Asian (EAS) AF: 0.876 AC: 4532 AN: 5174

South Asian (SAS) AF: 0.696 AC: 3358 AN: 4824

European-Finnish (FIN) AF: 0.599 AC: 6345 AN: 10584

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38499 AN: 67982

Other (OTH) AF: 0.491 AC: 1038 AN: 2112

Alfa AF: 0.501 Hom.: 2626

Bravo AF: 0.449

Asia WGS AF: 0.726 AC: 2524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.81
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1236; hg19: chr12-131274394;