12-130806556-C-T

Variant names:

• chr12-130806556-C-T
• rs7301826
• NM_194356.4:c.463+426G>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.463+426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,010 control chromosomes in the GnomAD database, including 20,602 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 0.50 (20602 hom., cov: 32)
• Consequence: STX2 NM_194356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 19 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194356.4. 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
	STX2	NM_194356.4	MANE Select	c.463+426G>A		intron	N/A	NP_919337.1
	STX2	NM_001413775.1		c.463+426G>A		intron	N/A	NP_001400704.1
	STX2	NM_001980.5		c.463+426G>A		intron	N/A	NP_001971.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX2	ENST00000392373.7	TSL:5 MANE Select	c.463+426G>A		intron	N/A	ENSP00000376178.2
	STX2	ENST00000261653.11	TSL:1	c.463+426G>A		intron	N/A	ENSP00000261653.6
	STX2	ENST00000926399.1		c.475+426G>A		intron	N/A	ENSP00000596458.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75303 AN: 151892 Hom.: 20606 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.495 AC: 75314 AN: 152010 Hom.: 20602 Cov.: 32 AF XY: 0.503 AC XY: 37390 AN XY: 74278

African (AFR) AF: 0.263 AC: 10897 AN: 41480

American (AMR) AF: 0.553 AC: 8457 AN: 15286

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

East Asian (EAS) AF: 0.873 AC: 4505 AN: 5162

South Asian (SAS) AF: 0.694 AC: 3341 AN: 4816

European-Finnish (FIN) AF: 0.597 AC: 6293 AN: 10544

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

European-Non Finnish (NFE) AF: 0.566 AC: 38468 AN: 67934

Other (OTH) AF: 0.512 AC: 1082 AN: 2114

Alfa AF: 0.550 Hom.: 36182

Bravo AF: 0.482

Asia WGS AF: 0.728 AC: 2531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.58
PhyloP100		-0.17
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: rs7301826; hg19: chr12-131291101;