rs9392056

chr6-518078-G-Achr6-518078-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018303.6(EXOC2):c.2380+14391C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,070 control chromosomes in the GnomAD database, including 20,265 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 0.48 (20265 hom., cov: 33)
• Consequence: EXOC2 NM_018303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

Genes affected

EXOC2 (HGNC:24968): (exocyst complex component 2) The protein encoded by this gene is a component of the exocyst complex, a multi-protein complex essential for the polarized targeting of exocytic vesicles to specific docking sites on the plasma membrane. Though best characterized in yeast, the component proteins and the functions of the exocyst complex have been demonstrated to be highly conserved in higher eukaryotes. At least eight components of the exocyst complex, including this protein, are found to interact with the actin cytoskeletal remodeling and vesicle transport machinery. This interaction has been shown to mediate filopodia formation in fibroblasts. This protein has been shown to interact with the Ral subfamily of GTPases and thereby mediate exocytosis by tethering vesicles to the plasma membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC2	NM_018303.6	c.2380+14391C>T		intron_variant		ENST00000230449.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC2	ENST00000230449.9	c.2380+14391C>T		intron_variant		1	NM_018303.6	P1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73257 AN: 151952 Hom.: 20259 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.482 AC: 73285 AN: 152070 Hom.: 20265 Cov.: 33 AF XY: 0.484 AC XY: 35971 AN XY: 74336

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.517

Alfa AF: 0.588 Hom.: 34265

Bravo AF: 0.463

Asia WGS AF: 0.561 AC: 1949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.0
Dann	Benign	0.80

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: rs9392056; hg19: chr6-518078;