17-15974911-T-A

Variant names:

• chr17-15974911-T-A
• rs1225430587
• NM_000676.4:c.568T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000676.4(ADORA2B):​c.568T>A​(p.Cys190Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C190G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADORA2B NM_000676.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.867

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000676.4. 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
	ADORA2B	NM_000676.4	MANE Select	c.568T>A	p.Cys190Ser	missense	Exon 2 of 2	NP_000667.1	P29275

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA2B	ENST00000304222.3	TSL:1 MANE Select	c.568T>A	p.Cys190Ser	missense	Exon 2 of 2	ENSP00000304501.2	P29275
	ADORA2B	ENST00000582124.1	TSL:6	n.1049T>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	0.68	N
PhyloP100		8.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.025	D
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.85
MutPred		0.60		Loss of helix (P = 0.2271)
MVP		0.93
MPC		0.68
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.76
gMVP		0.80

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

Other links and lift over

dbSNP: rs1225430587; hg19: chr17-15878225;