2-72184067-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015189.3(EXOC6B):c.2309+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,483,166 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (8 hom.)
• Consequence: EXOC6B NM_015189.3 splice_region, intron
• Scores: Splicing: ADA: 0.0002356
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0290

Genes affected

EXOC6B (HGNC:17085): (exocyst complex component 6B) This gene encodes a protein which is a part of the evolutionarily conserved exocyst, a multimeric protein complex necessary for exocytosis, which in turn, is crucial for cell growth, polarity and migration. Disruption of this gene may be associated with phenotypes exhibiting multiple symptoms including intellectual disability and developmental delay (DD). [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 2-72184067-G-C is Benign according to our data. Variant chr2-72184067-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 713677.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC6B	NM_015189.3	c.2309+8C>G		splice_region_variant, intron_variant		ENST00000272427.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC6B	ENST00000272427.11	c.2309+8C>G		splice_region_variant, intron_variant		1	NM_015189.3	P4

Frequencies

GnomAD3 genomes AF: 0.00149 AC: 226 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00282

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00172 AC: 290 AN: 168516 Hom.: 2 AF XY: 0.00168 AC XY: 149 AN XY: 88798

Gnomad AFR exome AF: 0.000545

Gnomad AMR exome AF: 0.000119

Gnomad ASJ exome AF: 0.000115

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000871

Gnomad FIN exome AF: 0.000924

Gnomad NFE exome AF: 0.00353

Gnomad OTH exome AF: 0.000645

GnomAD4 exome AF: 0.00249 AC: 3319 AN: 1330962 Hom.: 8 Cov.: 21 AF XY: 0.00240 AC XY: 1586 AN XY: 661492

Gnomad4 AFR exome AF: 0.000658

Gnomad4 AMR exome AF: 0.000165

Gnomad4 ASJ exome AF: 0.0000806

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00110

Gnomad4 FIN exome AF: 0.00102

Gnomad4 NFE exome AF: 0.00303

Gnomad4 OTH exome AF: 0.00134

GnomAD4 genome AF: 0.00148 AC: 225 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74402

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00281

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00217 Hom.: 2

Bravo AF: 0.00137

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	3.9
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00024
dbscSNV1_RF	Benign	0.018
SpliceAI score (max)		0.010		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: rs189615828; hg19: chr2-72411196;