rs2493013

Variant names:

• chr6-516350-A-C
• rs2493013
• NM_018303.6:c.2380+16119T>G

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+16119T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,032 control chromosomes in the GnomAD database, including 36,906 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 0.69 (36906 hom., cov: 31)
• Consequence: EXOC2 NM_018303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC2	NM_018303.6	c.2380+16119T>G		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+16119T>G		intron_variant	Intron 23 of 27	1	NM_018303.6	ENSP00000230449.4

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104120 AN: 151914 Hom.: 36893 Cov.: 31

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.685 AC: 104170 AN: 152032 Hom.: 36906 Cov.: 31 AF XY: 0.682 AC XY: 50687 AN XY: 74314

African (AFR) AF: 0.527 AC: 21807 AN: 41408

American (AMR) AF: 0.742 AC: 11339 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2763 AN: 3470

East Asian (EAS) AF: 0.415 AC: 2145 AN: 5164

South Asian (SAS) AF: 0.542 AC: 2606 AN: 4808

European-Finnish (FIN) AF: 0.773 AC: 8184 AN: 10584

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53036 AN: 67996

Other (OTH) AF: 0.708 AC: 1494 AN: 2110

Alfa AF: 0.756 Hom.: 81069

Bravo AF: 0.677

Asia WGS AF: 0.486 AC: 1691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.39
PhyloP100		-0.59
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: rs2493013; hg19: chr6-516350;