NM_015189.3:c.2309+17A>G

Variant names:

• chr2-72184058-T-C
• rs141623406
• NM_015189.3:c.2309+17A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

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.2309+17A>G		intron	N/A	NP_056004.1	Q9Y2D4-1
	EXOC6B	NM_001321729.2		c.2309+17A>G		intron	N/A	NP_001308658.1	A0A0U1RRB6
	EXOC6B	NM_001321731.2		c.2309+17A>G		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.2309+17A>G		intron	N/A	ENSP00000272427.7	Q9Y2D4-1
	EXOC6B	ENST00000971151.1		c.2381+17A>G		intron	N/A	ENSP00000641210.1
	EXOC6B	ENST00000971153.1		c.2342+17A>G		intron	N/A	ENSP00000641212.1

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

GnomAD2 exomes AF: 0.00164 AC: 270 AN: 164314 AF XY: 0.00132

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 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

African (AFR) AF: 0.0243 AC: 709 AN: 29206

American (AMR) AF: 0.00151 AC: 54 AN: 35842

Ashkenazi Jewish (ASJ) AF: 0.000982 AC: 24 AN: 24428

East Asian (EAS) AF: 0.0000282 AC: 1 AN: 35436

South Asian (SAS) AF: 0.000222 AC: 17 AN: 76462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49662

Middle Eastern (MID) AF: 0.000916 AC: 5 AN: 5460

European-Non Finnish (NFE) AF: 0.0000548 AC: 53 AN: 966324

Other (OTH) AF: 0.00169 AC: 91 AN: 53988

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

African (AFR) AF: 0.0250 AC: 1039 AN: 41526

American (AMR) AF: 0.00307 AC: 47 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000832 AC: 4 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68014

Other (OTH) AF: 0.00474 AC: 10 AN: 2108

Alfa AF: 0.00384 Hom.: 1

Bravo AF: 0.00858

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.67
PhyloP100		0.99
Mutation Taster		=100/0	polymorphism

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: rs141623406; hg19: chr2-72411187;