17-15974932-A-C

Position:

• chr17-15974932-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000676.4(ADORA2B):​c.589A>C​(p.Ile197Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADORA2B NM_000676.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26

Genes affected

ADORA2B (HGNC:264): (adenosine A2b receptor) This gene encodes an adenosine receptor that is a member of the G protein-coupled receptor superfamily. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. This protein also interacts with netrin-1, which is involved in axon elongation. The gene is located near the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19331133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADORA2B	NM_000676.4	c.589A>C	p.Ile197Leu	missense_variant	2/2	ENST00000304222.3	NP_000667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADORA2B	ENST00000304222.3	c.589A>C	p.Ile197Leu	missense_variant	2/2	1	NM_000676.4	ENSP00000304501.2
ADORA2B	ENST00000582124.1	n.1070A>C		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 09, 2024

The c.589A>C (p.I197L) alteration is located in exon 2 (coding exon 2) of the ADORA2B gene. This alteration results from a A to C substitution at nucleotide position 589, causing the isoleucine (I) at amino acid position 197 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.068
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	0.84	T
Polyphen		0.024	B
Vest4		0.40
MutPred		0.49		Gain of catalytic residue at I197 (P = 0.0055);
MVP		0.62
MPC		0.57
ClinPred		0.57	D
GERP RS		5.6
Varity_R		0.27
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-15878246;