rs2493040

chr6-535839-G-Achr6-535839-G-Cchr6-535839-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EXOC2	NM_018303.6	c.2239-3229C>T		intron_variant		ENST00000230449.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC2	ENST00000230449.9	c.2239-3229C>T		intron_variant		1	NM_018303.6	P1

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

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.450

Alfa AF: 0.339 Hom.: 12435

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2493040; hg19: chr6-535839;