rs1237777829

Variant names:

• chr2-72184204-C-A
• rs1237777829
• NM_015189.3:c.2197-17G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-72184204-C-A
• chr2-72184204-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_015189.3(EXOC6B):​c.2197-17G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,403,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: EXOC6B NM_015189.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.214
• Publications: 0 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• spondyloepimetaphyseal dysplasia with joint laxity

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 2-72184204-C-A is Benign according to our data. Variant chr2-72184204-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1911065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000525 (8/152270) while in subpopulation EAS AF = 0.000965 (5/5182). AF 95% confidence interval is 0.00038. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.2197-17G>T		intron	N/A	NP_056004.1	Q9Y2D4-1
	EXOC6B	NM_001321729.2		c.2197-17G>T		intron	N/A	NP_001308658.1	A0A0U1RRB6
	EXOC6B	NM_001321731.2		c.2197-17G>T		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.2197-17G>T		intron	N/A	ENSP00000272427.7	Q9Y2D4-1
	EXOC6B	ENST00000971151.1		c.2269-17G>T		intron	N/A	ENSP00000641210.1
	EXOC6B	ENST00000971153.1		c.2230-17G>T		intron	N/A	ENSP00000641212.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000572 AC: 9 AN: 157272 AF XY: 0.0000605

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000644

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000256 AC: 32 AN: 1251348 Hom.: 0 Cov.: 19 AF XY: 0.0000320 AC XY: 20 AN XY: 624628

African (AFR) AF: 0.00 AC: 0 AN: 28670

American (AMR) AF: 0.00 AC: 0 AN: 35404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24204

East Asian (EAS) AF: 0.000344 AC: 12 AN: 34920

South Asian (SAS) AF: 0.000145 AC: 11 AN: 75882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5446

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 944350

Other (OTH) AF: 0.000169 AC: 9 AN: 53130

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely 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	-0.54
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		-0.21

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: rs1237777829; hg19: chr2-72411333;