chr19-14397922-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_078481.4(ADGRE5):c.806G>C(p.Gly269Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 18)
Exomes 𝑓: 8.1e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ADGRE5
NM_078481.4 missense
NM_078481.4 missense
Scores
4
13
Clinical Significance
Conservation
PhyloP100: -0.124
Genes affected
ADGRE5 (HGNC:1711): (adhesion G protein-coupled receptor E5) This gene encodes a member of the EGF-TM7 subfamily of adhesion G protein-coupled receptors, which mediate cell-cell interactions. These proteins are cleaved by self-catalytic proteolysis into a large extracellular subunit and seven-span transmembrane subunit, which associate at the cell surface as a receptor complex. The encoded protein may play a role in cell adhesion as well as leukocyte recruitment, activation and migration, and contains multiple extracellular EGF-like repeats which mediate binding to chondroitin sulfate and the cell surface complement regulatory protein CD55. Expression of this gene may play a role in the progression of several types of cancer. Alternatively spliced transcript variants encoding multiple isoforms with 3 to 5 EGF-like repeats have been observed for this gene. This gene is found in a cluster with other EGF-TM7 genes on the short arm of chromosome 19. [provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.22485948).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRE5 | NM_078481.4 | c.806G>C | p.Gly269Ala | missense_variant | 8/20 | ENST00000242786.6 | |
ADGRE5 | NM_001025160.3 | c.659G>C | p.Gly220Ala | missense_variant | 7/19 | ||
ADGRE5 | NM_001784.6 | c.527G>C | p.Gly176Ala | missense_variant | 6/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRE5 | ENST00000242786.6 | c.806G>C | p.Gly269Ala | missense_variant | 8/20 | 1 | NM_078481.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 18
GnomAD3 genomes
?
Cov.:
18
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.10e-7 AC: 1AN: 1234254Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 616216
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1234254
Hom.:
Cov.:
22
AF XY:
AC XY:
0
AN XY:
616216
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 18
GnomAD4 genome
?
Cov.:
18
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 23, 2023 | The c.806G>C (p.G269A) alteration is located in exon 8 (coding exon 8) of the ADGRE5 gene. This alteration results from a G to C substitution at nucleotide position 806, causing the glycine (G) at amino acid position 269 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;T;T
Sift4G
Benign
T;T;T
Vest4
MutPred
0.48
.;.;Gain of glycosylation at P267 (P = 0.1148);
MVP
MPC
2.8
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.