chr12-131005989-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_198827.5(ADGRD1):c.1273G>A(p.Gly425Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000887 in 1,611,730 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000093 ( 0 hom. )
Consequence
ADGRD1
NM_198827.5 missense
NM_198827.5 missense
Scores
1
8
9
Clinical Significance
Conservation
PhyloP100: 3.59
Genes affected
ADGRD1 (HGNC:19893): (adhesion G protein-coupled receptor D1) The adhesion G-protein-coupled receptors (GPCRs), including GPR133, are membrane-bound proteins with long N termini containing multiple domains. GPCRs, or GPRs, contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins (summary by Bjarnadottir et al., 2004 [PubMed 15203201]).[supplied by OMIM, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRD1 | NM_198827.5 | c.1273G>A | p.Gly425Ser | missense_variant | 12/25 | ENST00000261654.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRD1 | ENST00000261654.10 | c.1273G>A | p.Gly425Ser | missense_variant | 12/25 | 1 | NM_198827.5 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152076Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249876Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135106
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GnomAD4 exome AF: 0.0000932 AC: 136AN: 1459654Hom.: 0 Cov.: 32 AF XY: 0.0000895 AC XY: 65AN XY: 726112
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152076Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74278
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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 | Jul 13, 2021 | The c.1273G>A (p.G425S) alteration is located in exon 12 (coding exon 12) of the ADGRD1 gene. This alteration results from a G to A substitution at nucleotide position 1273, causing the glycine (G) at amino acid position 425 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;D
Sift4G
Pathogenic
D;D
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at