5-7402448-G-T

Variant names:

• chr5-7402448-G-T
• rs10512920
• NM_020546.3:c.210+5942G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020546.3(ADCY2):​c.210+5942G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,020 control chromosomes in the GnomAD database, including 7,735 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 0.31 (7735 hom., cov: 33)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763
• Publications: 5 publications found

Genes affected

ADCY2 (HGNC:233): (adenylate cyclase 2) This gene encodes a member of the family of adenylate cyclases, which are membrane-associated enzymes that catalyze the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This enzyme is insensitive to Ca(2+)/calmodulin, and is stimulated by the G protein beta and gamma subunit complex. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020546.3. 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
	ADCY2	NM_020546.3	MANE Select	c.210+5942G>T		intron	N/A	NP_065433.2	Q08462-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY2	ENST00000338316.9	TSL:1 MANE Select	c.210+5942G>T		intron	N/A	ENSP00000342952.4	Q08462-1
	ADCY2	ENST00000915366.1		c.210+5942G>T		intron	N/A	ENSP00000585425.1
	ADCY2	ENST00000915369.1		c.210+5942G>T		intron	N/A	ENSP00000585428.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46393 AN: 151900 Hom.: 7721 Cov.: 33

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.0176

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.306 AC: 46449 AN: 152020 Hom.: 7735 Cov.: 33 AF XY: 0.299 AC XY: 22213 AN XY: 74298

African (AFR) AF: 0.414 AC: 17172 AN: 41444

American (AMR) AF: 0.178 AC: 2724 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 986 AN: 3472

East Asian (EAS) AF: 0.0176 AC: 91 AN: 5172

South Asian (SAS) AF: 0.228 AC: 1097 AN: 4818

European-Finnish (FIN) AF: 0.301 AC: 3177 AN: 10560

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20277 AN: 67976

Other (OTH) AF: 0.262 AC: 552 AN: 2104

Alfa AF: 0.283 Hom.: 10608

Bravo AF: 0.297

Asia WGS AF: 0.137 AC: 478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.66
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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: rs10512920; hg19: chr5-7402561;