rs10733669

Variant names:

• chr9-124457854-A-G
• rs10733669
• NM_001395425.1:c.1672+248A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395425.1(ADGRD2):​c.1672+248A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,126 control chromosomes in the GnomAD database, including 29,006 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (29006 hom., cov: 33)
• Consequence: ADGRD2 NM_001395425.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

Genes affected

ADGRD2 (HGNC:18651): (adhesion G protein-coupled receptor D2) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRD2	NM_001395425.1	c.1672+248A>G		intron_variant	Intron 11 of 24	ENST00000696331.1	NP_001382354.1
ADGRD2	XM_047423339.1	c.1672+248A>G		intron_variant	Intron 9 of 22		XP_047279295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRD2	ENST00000696331.1	c.1672+248A>G		intron_variant	Intron 11 of 24		NM_001395425.1	ENSP00000512565.1
ADGRD2	ENST00000639026.1	n.754+248A>G		intron_variant	Intron 5 of 12	1		ENSP00000492825.1
ADGRD2	ENST00000706946.1	c.1672+248A>G		intron_variant	Intron 11 of 24			ENSP00000516666.1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93287 AN: 152006 Hom.: 29006 Cov.: 33

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.638

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.613 AC: 93324 AN: 152126 Hom.: 29006 Cov.: 33 AF XY: 0.610 AC XY: 45357 AN XY: 74354

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.637

Alfa AF: 0.655 Hom.: 32682

Bravo AF: 0.614

Asia WGS AF: 0.531 AC: 1848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs10733669; hg19: chr9-127220133; COSMIC: COSV58340189; COSMIC: COSV58340189;