rs80011872

Variant names:

• chr6-499672-C-A
• rs80011872
• NM_018303.6:c.2409G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-499672-C-A
• chr6-499672-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_018303.6(EXOC2):​c.2409G>T​(p.Leu803Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,613,582 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (82 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (59 hom.)
• Consequence: EXOC2 NM_018303.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.11
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 6-499672-C-A is Benign according to our data. Variant chr6-499672-C-A is described in ClinVar as Benign. ClinVar VariationId is 789742.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.11 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018303.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC2	NM_018303.6	MANE Select	c.2409G>T	p.Leu803Leu	synonymous	Exon 24 of 28	NP_060773.3
	EXOC2	NR_073064.2		n.2735G>T		non_coding_transcript_exon	Exon 26 of 30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC2	ENST00000230449.9	TSL:1 MANE Select	c.2409G>T	p.Leu803Leu	synonymous	Exon 24 of 28	ENSP00000230449.4	Q96KP1
	EXOC2	ENST00000930291.1		c.2511G>T	p.Leu837Leu	synonymous	Exon 25 of 29	ENSP00000600350.1
	EXOC2	ENST00000930294.1		c.2499G>T	p.Leu833Leu	synonymous	Exon 24 of 28	ENSP00000600353.1

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2465 AN: 151950 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00976

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00448 AC: 1126 AN: 251274 AF XY: 0.00317

Gnomad AFR exome AF: 0.0567

Gnomad AMR exome AF: 0.00431

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00157 AC: 2293 AN: 1461514 Hom.: 59 Cov.: 30 AF XY: 0.00127 AC XY: 926 AN XY: 727062

African (AFR) AF: 0.0499 AC: 1668 AN: 33428

American (AMR) AF: 0.00470 AC: 210 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5766

European-Non Finnish (NFE) AF: 0.000148 AC: 165 AN: 1111782

Other (OTH) AF: 0.00391 AC: 236 AN: 60372

GnomAD4 genome AF: 0.0162 AC: 2470 AN: 152068 Hom.: 82 Cov.: 32 AF XY: 0.0158 AC XY: 1173 AN XY: 74346

African (AFR) AF: 0.0547 AC: 2266 AN: 41436

American (AMR) AF: 0.00975 AC: 149 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 67996

Other (OTH) AF: 0.0118 AC: 25 AN: 2110

Alfa AF: 0.00725 Hom.: 30

Bravo AF: 0.0186

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000534

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		2.1
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: rs80011872; hg19: chr6-499672;