ADGRD1 p.Ile280Leu

Variant names:

• chr12-130992264-A-T
• NM_198827.5:c.838A>T
• ADGRD1 p.Ile280Leu

Your query was ambiguous. Multiple possible variants found:

• chr12-130992264-A-T
• chr12-130992264-A-C
• chr12-130992264-ATA-TTG
• chr12-130992264-ATA-CTT
• chr12-130992264-ATA-CTC
• chr12-130992264-ATA-CTG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198827.5(ADGRD1):​c.838A>T​(p.Ile280Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I280V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRD1 NM_198827.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 0 publications found

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]

ADGRD1-AS1 (HGNC:53314): (ADGRD1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26999593).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198827.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRD1	NM_198827.5	MANE Select	c.838A>T	p.Ile280Leu	missense	Exon 8 of 25	NP_942122.2
	ADGRD1	NM_001330497.2		c.934A>T	p.Ile312Leu	missense	Exon 9 of 26	NP_001317426.1	Q6QNK2-4
	ADGRD1-AS1	NR_131950.1		n.277+85T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRD1	ENST00000261654.10	TSL:1 MANE Select	c.838A>T	p.Ile280Leu	missense	Exon 8 of 25	ENSP00000261654.5	Q6QNK2-1
	ADGRD1	ENST00000535015.5	TSL:1	c.934A>T	p.Ile312Leu	missense	Exon 9 of 26	ENSP00000444425.1	Q6QNK2-4
	ADGRD1	ENST00000881063.1		c.838A>T	p.Ile280Leu	missense	Exon 8 of 26	ENSP00000551122.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Benign	0.023
Eigen_PC	Benign	0.0011
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.99	T
PhyloP100		1.9
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.18
Sift	Benign	0.063	T
Sift4G	Uncertain	0.021	D
Varity_R		0.10
gMVP		0.40
Mutation Taster		=87/13	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-131476809;