rs6918152

Variant names:

• chr6-542159-A-G
• rs6918152
• NM_018303.6:c.2238+7016T>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.2238+7016T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,160 control chromosomes in the GnomAD database, including 20,272 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 (20272 hom., cov: 33)
• Consequence: EXOC2 NM_018303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• Publications: 23 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018303.6. 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
	EXOC2	NM_018303.6	MANE Select	c.2238+7016T>C		intron	N/A	NP_060773.3
	EXOC2	NR_073064.2		n.2564+7016T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC2	ENST00000230449.9	TSL:1 MANE Select	c.2238+7016T>C		intron	N/A	ENSP00000230449.4	Q96KP1
	EXOC2	ENST00000930291.1		c.2238+7016T>C		intron	N/A	ENSP00000600350.1
	EXOC2	ENST00000930294.1		c.2328+7016T>C		intron	N/A	ENSP00000600353.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73138 AN: 152042 Hom.: 20266 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.481 AC: 73166 AN: 152160 Hom.: 20272 Cov.: 33 AF XY: 0.483 AC XY: 35914 AN XY: 74390

African (AFR) AF: 0.187 AC: 7759 AN: 41512

American (AMR) AF: 0.512 AC: 7825 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2185 AN: 3468

East Asian (EAS) AF: 0.477 AC: 2467 AN: 5176

South Asian (SAS) AF: 0.707 AC: 3403 AN: 4816

European-Finnish (FIN) AF: 0.572 AC: 6049 AN: 10584

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

European-Non Finnish (NFE) AF: 0.615 AC: 41793 AN: 68008

Other (OTH) AF: 0.514 AC: 1085 AN: 2110

Alfa AF: 0.569 Hom.: 93355

Bravo AF: 0.462

Asia WGS AF: 0.560 AC: 1948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		-0.70
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: rs6918152; hg19: chr6-542159;