2-72184159-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015189.3(EXOC6B):​c.2225G>T​(p.Trp742Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

EXOC6B
NM_015189.3 missense

Scores

9
7
3

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.91
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EXOC6BNM_015189.3 linkuse as main transcriptc.2225G>T p.Trp742Leu missense_variant 21/22 ENST00000272427.11 NP_056004.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EXOC6BENST00000272427.11 linkuse as main transcriptc.2225G>T p.Trp742Leu missense_variant 21/221 NM_015189.3 ENSP00000272427 P4Q9Y2D4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1405394
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
693936
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

EXOC6B-related disorder Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesDec 28, 2023The EXOC6B c.2225G>T variant is predicted to result in the amino acid substitution p.Trp742Leu. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
32
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T;.
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.85
D;D
MetaSVM
Benign
-0.80
T
MutationAssessor
Pathogenic
3.0
M;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-11
D;.
REVEL
Uncertain
0.49
Sift
Uncertain
0.0020
D;.
Sift4G
Uncertain
0.0060
D;D
Polyphen
0.99
D;.
Vest4
0.70
MutPred
0.79
Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP
0.57
MPC
2.4
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.80
gMVP
0.65

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-72411288; API