rs142684762

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_201525.4(ADGRG1):ā€‹c.1352A>Gā€‹(p.Asp451Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ADGRG1
NM_201525.4 missense

Scores

4
10
4

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.03
Variant links:
Genes affected
ADGRG1 (HGNC:4512): (adhesion G protein-coupled receptor G1) This gene encodes a member of the G protein-coupled receptor family and regulates brain cortical patterning. The encoded protein binds specifically to transglutaminase 2, a component of tissue and tumor stroma implicated as an inhibitor of tumor progression. Mutations in this gene are associated with a brain malformation known as bilateral frontoparietal polymicrogyria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

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;
PP5
Variant 16-57659478-A-G is Pathogenic according to our data. Variant chr16-57659478-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 520821.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADGRG1NM_201525.4 linkuse as main transcriptc.1352A>G p.Asp451Gly missense_variant 11/14 ENST00000562631.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADGRG1ENST00000562631.7 linkuse as main transcriptc.1352A>G p.Asp451Gly missense_variant 11/141 NM_201525.4 P4Q9Y653-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461568
Hom.:
0
Cov.:
35
AF XY:
0.00000275
AC XY:
2
AN XY:
727104
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
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
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingAmbry GeneticsNov 17, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.57
BayesDel_addAF
Uncertain
0.063
T
BayesDel_noAF
Benign
-0.15
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
.;T;T;.;.;.;.;.
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.87
.;.;D;.;D;.;.;D
M_CAP
Uncertain
0.18
D
MetaRNN
Uncertain
0.73
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.033
T
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-2.4
N;N;N;N;.;N;N;N
REVEL
Benign
0.28
Sift
Uncertain
0.021
D;D;D;D;.;D;D;D
Sift4G
Uncertain
0.027
D;D;D;D;D;D;D;D
Polyphen
0.94
P;D;D;P;.;P;P;P
Vest4
0.59
MVP
0.96
ClinPred
0.97
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.75
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142684762; hg19: chr16-57693390; API