2-72263190-G-T

Position:

• chr2-72263190-G-T

Variant summary

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

The NM_015189.3(EXOC6B):​c.2196+71757C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,026 control chromosomes in the GnomAD database, including 21,019 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 0.46 (21018 hom., cov: 32)
  • Exomes 𝑓: 0.36 (1 hom.)
• Consequence: EXOC6B NM_015189.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC6B	NM_015189.3	c.2196+71757C>A		intron_variant		ENST00000272427.11	NP_056004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC6B	ENST00000272427.11	c.2196+71757C>A		intron_variant		1	NM_015189.3	ENSP00000272427.7

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69525 AN: 151894 Hom.: 20958 Cov.: 32

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0284

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.357 AC: 5 AN: 14 Hom.: 1 AF XY: 0.500 AC XY: 5 AN XY: 10

Gnomad4 AFR exome AF: 1.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.458 AC: 69649 AN: 152012 Hom.: 21018 Cov.: 32 AF XY: 0.447 AC XY: 33199 AN XY: 74296

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.0285

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.405

Alfa AF: 0.384 Hom.: 2298

Bravo AF: 0.481

Asia WGS AF: 0.143 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.62
DANN	Benign	0.72

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: rs6546753; hg19: chr2-72490319;