6-562803-T-C

Variant names:

• chr6-562803-T-C
• rs775909803
• NM_018303.6:c.1832A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018303.6(EXOC2):​c.1832A>G​(p.Asn611Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000553 in 1,447,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: EXOC2 NM_018303.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12428874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC2	NM_018303.6	c.1832A>G	p.Asn611Ser	missense_variant	Exon 17 of 28	ENST00000230449.9	NP_060773.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC2	ENST00000230449.9	c.1832A>G	p.Asn611Ser	missense_variant	Exon 17 of 28	1	NM_018303.6	ENSP00000230449.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000828 AC: 2 AN: 241592 AF XY: 0.00000767

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000553 AC: 8 AN: 1447772 Hom.: 0 Cov.: 28 AF XY: 0.00000417 AC XY: 3 AN XY: 719270

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 32966

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 42572

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25820

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39344

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 81546

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53178

Gnomad4 NFE exome AF: 0.00000723 AC: 8 AN: 1106736

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 59912

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1832A>G (p.N611S) alteration is located in exon 17 (coding exon 16) of the EXOC2 gene. This alteration results from a A to G substitution at nucleotide position 1832, causing the asparagine (N) at amino acid position 611 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.11
Sift	Benign	0.17	T
Sift4G	Benign	0.11	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.49		Loss of catalytic residue at N611 (P = 7e-04);
MVP		0.27
MPC		0.14
ClinPred		0.55	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.088
Mutation Taster		=87/13	polymorphism

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: rs775909803; hg19: chr6-562803;