6-566741-A-G

Variant names:

• chr6-566741-A-G
• rs2476842
• NM_018303.6:c.1444-1812T>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.1444-1812T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,900 control chromosomes in the GnomAD database, including 25,309 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 0.57 (25309 hom., cov: 31)
• Consequence: EXOC2 NM_018303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.793
• Publications: 11 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC2	NM_018303.6	MANE Select	c.1444-1812T>C		intron	N/A	NP_060773.3
	EXOC2	NR_073064.2		n.1770-1812T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC2	ENST00000230449.9	TSL:1 MANE Select	c.1444-1812T>C		intron	N/A	ENSP00000230449.4

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86539 AN: 151782 Hom.: 25269 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.570 AC: 86630 AN: 151900 Hom.: 25309 Cov.: 31 AF XY: 0.567 AC XY: 42092 AN XY: 74242

African (AFR) AF: 0.684 AC: 28318 AN: 41418

American (AMR) AF: 0.497 AC: 7603 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1824 AN: 3468

East Asian (EAS) AF: 0.713 AC: 3675 AN: 5156

South Asian (SAS) AF: 0.468 AC: 2240 AN: 4790

European-Finnish (FIN) AF: 0.535 AC: 5637 AN: 10534

Middle Eastern (MID) AF: 0.438 AC: 127 AN: 290

European-Non Finnish (NFE) AF: 0.523 AC: 35527 AN: 67938

Other (OTH) AF: 0.519 AC: 1090 AN: 2102

Alfa AF: 0.541 Hom.: 46617

Bravo AF: 0.578

Asia WGS AF: 0.562 AC: 1957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.6
DANN	Benign	0.74
PhyloP100		0.79
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: rs2476842; hg19: chr6-566741;