rs9504361

Variant names:

• chr6-577820-A-G
• rs9504361
• NM_018303.6:c.1193-938T>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.1193-938T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,006 control chromosomes in the GnomAD database, including 12,911 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 0.40 (12911 hom., cov: 32)
• Consequence: EXOC2 NM_018303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 40 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 (AMR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC2	NM_018303.6	c.1193-938T>C		intron_variant	Intron 11 of 27	ENST00000230449.9	NP_060773.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC2	ENST00000230449.9	c.1193-938T>C		intron_variant	Intron 11 of 27	1	NM_018303.6	ENSP00000230449.4

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61486 AN: 151888 Hom.: 12897 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.405 AC: 61527 AN: 152006 Hom.: 12911 Cov.: 32 AF XY: 0.406 AC XY: 30139 AN XY: 74306

African (AFR) AF: 0.304 AC: 12601 AN: 41448

American (AMR) AF: 0.494 AC: 7558 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1755 AN: 3466

East Asian (EAS) AF: 0.239 AC: 1239 AN: 5176

South Asian (SAS) AF: 0.395 AC: 1901 AN: 4818

European-Finnish (FIN) AF: 0.433 AC: 4571 AN: 10554

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30534 AN: 67942

Other (OTH) AF: 0.458 AC: 965 AN: 2106

Alfa AF: 0.432 Hom.: 24682

Bravo AF: 0.402

Asia WGS AF: 0.324 AC: 1125 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	1.2
DANN	Benign	0.78
PhyloP100		0.12
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: rs9504361; hg19: chr6-577820;