2-72184058-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015189.3(EXOC6B):c.2309+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,429,002 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0073 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (12 hom.)
• Consequence: EXOC6B NM_015189.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.995

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-72184058-T-C is Benign according to our data. Variant chr2-72184058-T-C is described in ClinVar as [Benign]. Clinvar id is 1561857.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00729 (1110/152194) while in subpopulation AFR AF= 0.025 (1039/41526). AF 95% confidence interval is 0.0238. There are 14 homozygotes in gnomad4. There are 517 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC6B	NM_015189.3	c.2309+17A>G		intron_variant		ENST00000272427.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC6B	ENST00000272427.11	c.2309+17A>G		intron_variant		1	NM_015189.3	P4

Frequencies

GnomAD3 genomes AF: 0.00723 AC: 1099 AN: 152076 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00164 AC: 270 AN: 164314 Hom.: 6 AF XY: 0.00132 AC XY: 114 AN XY: 86496

Gnomad AFR exome AF: 0.0238

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000220

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000747 AC: 954 AN: 1276808 Hom.: 12 Cov.: 18 AF XY: 0.000656 AC XY: 418 AN XY: 637182

Gnomad4 AFR exome AF: 0.0243

Gnomad4 AMR exome AF: 0.00151

Gnomad4 ASJ exome AF: 0.000982

Gnomad4 EAS exome AF: 0.0000282

Gnomad4 SAS exome AF: 0.000222

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000548

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome AF: 0.00729 AC: 1110 AN: 152194 Hom.: 14 Cov.: 32 AF XY: 0.00695 AC XY: 517 AN XY: 74414

Gnomad4 AFR AF: 0.0250

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000832

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00384 Hom.: 1

Bravo AF: 0.00858

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 09, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	6.6
Dann	Benign	0.67

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: rs141623406; hg19: chr2-72411187;