12-130992264-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_198827.5(ADGRD1):āc.838A>Cā(p.Ile280Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I280V) has been classified as Uncertain significance.
Frequency
Consequence
NM_198827.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRD1 | NM_198827.5 | c.838A>C | p.Ile280Leu | missense_variant | 8/25 | ENST00000261654.10 | |
ADGRD1-AS1 | NR_131951.1 | n.70-1127T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRD1 | ENST00000261654.10 | c.838A>C | p.Ile280Leu | missense_variant | 8/25 | 1 | NM_198827.5 | P4 | |
ADGRD1-AS1 | ENST00000542980.1 | n.277+85T>G | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250806Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135532
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461184Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726826
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 26, 2023 | The c.838A>C (p.I280L) alteration is located in exon 8 (coding exon 8) of the ADGRD1 gene. This alteration results from a A to C substitution at nucleotide position 838, causing the isoleucine (I) at amino acid position 280 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at