chr2-72176719-T-C

Variant names:

• chr2-72176719-T-C
• rs41417
• NM_015189.3:c.*2616A>G

Variant summary

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

The NM_015189.3(EXOC6B):​c.*2616A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,198 control chromosomes in the GnomAD database, including 1,900 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 0.14 (1899 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: EXOC6B NM_015189.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 5 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: STRONG Submitted by: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC6B	NM_015189.3	c.*2616A>G		3_prime_UTR_variant	Exon 22 of 22	ENST00000272427.11	NP_056004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC6B	ENST00000272427.11	c.*2616A>G		3_prime_UTR_variant	Exon 22 of 22	1	NM_015189.3	ENSP00000272427.7

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21237 AN: 152076 Hom.: 1898 Cov.: 32

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.0243

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.140 AC: 21239 AN: 152194 Hom.: 1899 Cov.: 32 AF XY: 0.139 AC XY: 10372 AN XY: 74398

African (AFR) AF: 0.0503 AC: 2091 AN: 41560

American (AMR) AF: 0.175 AC: 2674 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 345 AN: 3468

East Asian (EAS) AF: 0.0244 AC: 126 AN: 5170

South Asian (SAS) AF: 0.102 AC: 494 AN: 4820

European-Finnish (FIN) AF: 0.197 AC: 2086 AN: 10590

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12862 AN: 68006

Other (OTH) AF: 0.143 AC: 301 AN: 2108

Alfa AF: 0.152 Hom.: 882

Bravo AF: 0.133

Asia WGS AF: 0.0680 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.64
PhyloP100		-0.38
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: rs41417; hg19: chr2-72403848;