rs2493040

Variant names:

• chr6-535839-G-A
• rs2493040
• NM_018303.6:c.2239-3229C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-535839-G-A
• chr6-535839-G-C
• chr6-535839-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018303.6(EXOC2):​c.2239-3229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,996 control chromosomes in the GnomAD database, including 20,565 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 (20565 hom., cov: 33)
• Consequence: EXOC2 NM_018303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 9 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC2	NM_018303.6	c.2239-3229C>T		intron_variant	Intron 22 of 27	ENST00000230449.9	NP_060773.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC2	ENST00000230449.9	c.2239-3229C>T		intron_variant	Intron 22 of 27	1	NM_018303.6	ENSP00000230449.4

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72203 AN: 151878 Hom.: 20528 Cov.: 33

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.476 AC: 72293 AN: 151996 Hom.: 20565 Cov.: 33 AF XY: 0.474 AC XY: 35216 AN XY: 74286

African (AFR) AF: 0.803 AC: 33293 AN: 41480

American (AMR) AF: 0.447 AC: 6828 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1236 AN: 3466

East Asian (EAS) AF: 0.522 AC: 2700 AN: 5168

South Asian (SAS) AF: 0.259 AC: 1249 AN: 4820

European-Finnish (FIN) AF: 0.370 AC: 3898 AN: 10522

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21599 AN: 67946

Other (OTH) AF: 0.450 AC: 948 AN: 2108

Alfa AF: 0.357 Hom.: 18195

Bravo AF: 0.498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.21
DANN	Benign	0.35
PhyloP100		-1.1
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: rs2493040; hg19: chr6-535839;