rs9392056

Variant names:

• chr6-518078-G-A
• rs9392056
• NM_018303.6:c.2380+14391C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-518078-G-A
• chr6-518078-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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]

EXOC2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EXOC2	NM_018303.6	c.2380+14391C>T		intron_variant	Intron 23 of 27	ENST00000230449.9	NP_060773.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC2	ENST00000230449.9	c.2380+14391C>T		intron_variant	Intron 23 of 27	1	NM_018303.6	ENSP00000230449.4

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

African (AFR) AF: 0.192 AC: 7961 AN: 41468

American (AMR) AF: 0.514 AC: 7855 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2167 AN: 3470

East Asian (EAS) AF: 0.477 AC: 2473 AN: 5180

South Asian (SAS) AF: 0.706 AC: 3403 AN: 4818

European-Finnish (FIN) AF: 0.574 AC: 6051 AN: 10548

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41682 AN: 67988

Other (OTH) AF: 0.517 AC: 1093 AN: 2114

Alfa AF: 0.575 Hom.: 44222

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
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: rs9392056; hg19: chr6-518078;