rs764900952

Variant names:

• chr2-72184110-C-A
• rs764900952
• NM_015189.3:c.2274G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-72184110-C-A
• chr2-72184110-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015189.3(EXOC6B):​c.2274G>T​(p.Arg758Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,413,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R758R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: EXOC6B NM_015189.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=-2.33 with no splicing effect.

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.2274G>T	p.Arg758Arg	synonymous	Exon 21 of 22	NP_056004.1	Q9Y2D4-1
	EXOC6B	NM_001321729.2		c.2274G>T	p.Arg758Arg	synonymous	Exon 21 of 23	NP_001308658.1	A0A0U1RRB6
	EXOC6B	NM_001321731.2		c.2274G>T	p.Arg758Arg	synonymous	Exon 21 of 23	NP_001308660.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC6B	ENST00000272427.11	TSL:1 MANE Select	c.2274G>T	p.Arg758Arg	synonymous	Exon 21 of 22	ENSP00000272427.7	Q9Y2D4-1
	EXOC6B	ENST00000971151.1		c.2346G>T	p.Arg782Arg	synonymous	Exon 22 of 24	ENSP00000641210.1
	EXOC6B	ENST00000971153.1		c.2307G>T	p.Arg769Arg	synonymous	Exon 21 of 23	ENSP00000641212.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1413680 Hom.: 0 Cov.: 29 AF XY: 0.00000143 AC XY: 1 AN XY: 698554

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32242

American (AMR) AF: 0.00 AC: 0 AN: 37600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25348

East Asian (EAS) AF: 0.00 AC: 0 AN: 37072

South Asian (SAS) AF: 0.00 AC: 0 AN: 79976

European-Finnish (FIN) AF: 0.0000198 AC: 1 AN: 50512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086472

Other (OTH) AF: 0.00 AC: 0 AN: 58744

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	4.9
DANN	Benign	0.61
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs764900952; hg19: chr2-72411239;