rs7761186

Variant names:

• chr6-512951-T-C
• rs7761186
• NM_018303.6:c.2381-13251A>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.2381-13251A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0617 in 152,260 control chromosomes in the GnomAD database, including 683 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 0.062 (683 hom., cov: 33)
• Consequence: EXOC2 NM_018303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC2	NM_018303.6	c.2381-13251A>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.2381-13251A>G		intron_variant	Intron 23 of 27	1	NM_018303.6	ENSP00000230449.4

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9356 AN: 152142 Hom.: 676 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0617 AC: 9390 AN: 152260 Hom.: 683 Cov.: 33 AF XY: 0.0619 AC XY: 4610 AN XY: 74454

African (AFR) AF: 0.141 AC: 5861 AN: 41536

American (AMR) AF: 0.0384 AC: 587 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.271 AC: 1403 AN: 5186

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4828

European-Finnish (FIN) AF: 0.0106 AC: 112 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0165 AC: 1120 AN: 68016

Other (OTH) AF: 0.0545 AC: 115 AN: 2112

Alfa AF: 0.0421 Hom.: 58

Bravo AF: 0.0705

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.5
DANN	Benign	0.61
PhyloP100		1.2
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: rs7761186; hg19: chr6-512951;