chr2-72728612-A-T

Variant names:

• chr2-72728612-A-T
• rs1508061
• NM_015189.3:c.464+2395T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015189.3(EXOC6B):​c.464+2395T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,092 control chromosomes in the GnomAD database, including 34,898 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 0.61 (34898 hom., cov: 31)
• Consequence: EXOC6B NM_015189.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• spondyloepimetaphyseal dysplasia with joint laxity, type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• spondyloepimetaphyseal dysplasia with joint laxity

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015189.3. 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
	EXOC6B	NM_015189.3	MANE Select	c.464+2395T>A		intron	N/A	NP_056004.1	Q9Y2D4-1
	EXOC6B	NM_001321729.2		c.464+2395T>A		intron	N/A	NP_001308658.1	A0A0U1RRB6
	EXOC6B	NM_001321731.2		c.464+2395T>A		intron	N/A	NP_001308660.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC6B	ENST00000272427.11	TSL:1 MANE Select	c.464+2395T>A		intron	N/A	ENSP00000272427.7	Q9Y2D4-1
	EXOC6B	ENST00000410104.1	TSL:1	c.464+2395T>A		intron	N/A	ENSP00000386698.1	J3QT38
	EXOC6B	ENST00000971151.1		c.536+2395T>A		intron	N/A	ENSP00000641210.1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93332 AN: 151974 Hom.: 34904 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.902

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.614 AC: 93330 AN: 152092 Hom.: 34898 Cov.: 31 AF XY: 0.626 AC XY: 46538 AN XY: 74334

African (AFR) AF: 0.159 AC: 6580 AN: 41476

American (AMR) AF: 0.750 AC: 11447 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2811 AN: 3472

East Asian (EAS) AF: 0.990 AC: 5103 AN: 5156

South Asian (SAS) AF: 0.903 AC: 4354 AN: 4820

European-Finnish (FIN) AF: 0.811 AC: 8588 AN: 10594

Middle Eastern (MID) AF: 0.784 AC: 229 AN: 292

European-Non Finnish (NFE) AF: 0.767 AC: 52159 AN: 67992

Other (OTH) AF: 0.657 AC: 1383 AN: 2106

Alfa AF: 0.673 Hom.: 4794

Bravo AF: 0.587

Asia WGS AF: 0.879 AC: 3055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.9
DANN	Benign	0.73
PhyloP100		1.6
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: rs1508061; hg19: chr2-72955741;