chr6-632061-G-C

Variant names:

• chr6-632061-G-C
• rs9328331
• NM_018303.6:c.295+880C>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.295+880C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,076 control chromosomes in the GnomAD database, including 37,696 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 0.70 (37696 hom., cov: 33)
• Consequence: EXOC2 NM_018303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC2	NM_018303.6	c.295+880C>G		intron_variant	Intron 3 of 27	ENST00000230449.9	NP_060773.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC2	ENST00000230449.9	c.295+880C>G		intron_variant	Intron 3 of 27	1	NM_018303.6	ENSP00000230449.4
EXOC2	ENST00000443083.5	c.295+880C>G		intron_variant	Intron 5 of 5	3		ENSP00000406400.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106180 AN: 151958 Hom.: 37696 Cov.: 33

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.698 AC: 106217 AN: 152076 Hom.: 37696 Cov.: 33 AF XY: 0.696 AC XY: 51730 AN XY: 74342

African (AFR) AF: 0.588 AC: 24350 AN: 41430

American (AMR) AF: 0.714 AC: 10927 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2875 AN: 3472

East Asian (EAS) AF: 0.672 AC: 3482 AN: 5182

South Asian (SAS) AF: 0.668 AC: 3223 AN: 4822

European-Finnish (FIN) AF: 0.718 AC: 7576 AN: 10554

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51258 AN: 68000

Other (OTH) AF: 0.740 AC: 1562 AN: 2110

Alfa AF: 0.629 Hom.: 1852

Bravo AF: 0.695

Asia WGS AF: 0.675 AC: 2345 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0030
DANN	Benign	0.70
PhyloP100		-2.6
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: rs9328331; hg19: chr6-632061;