2-72562188-A-G

Position:

• chr2-72562188-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015189.3(EXOC6B):​c.847-2667T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,084 control chromosomes in the GnomAD database, including 58,118 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 0.87 (58118 hom., cov: 31)
• Consequence: EXOC6B NM_015189.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

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]

EXOC6B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC6B	NM_015189.3	c.847-2667T>C		intron_variant		ENST00000272427.11	NP_056004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC6B	ENST00000272427.11	c.847-2667T>C		intron_variant		1	NM_015189.3	ENSP00000272427.7
EXOC6B	ENST00000410104.1	c.847-2667T>C		intron_variant		1		ENSP00000386698.1
EXOC6B	ENST00000634650.1	c.847-2667T>C		intron_variant		5		ENSP00000489442.1
EXOC6B	ENST00000410112.6	n.*558-2667T>C		intron_variant		5		ENSP00000386634.2

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132670 AN: 151966 Hom.: 58090 Cov.: 31

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.894

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.873 AC: 132747 AN: 152084 Hom.: 58118 Cov.: 31 AF XY: 0.877 AC XY: 65171 AN XY: 74352

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.904

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.933

Gnomad4 FIN AF: 0.921

Gnomad4 NFE AF: 0.894

Gnomad4 OTH AF: 0.866

Alfa AF: 0.884 Hom.: 15458

Bravo AF: 0.867

Asia WGS AF: 0.945 AC: 3287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.86

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: rs12471136; hg19: chr2-72789317;