rs10512928

Variant names:

• chr5-7546298-C-T
• rs10512928
• NM_020546.3:c.570+25399C>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.570+25399C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,178 control chromosomes in the GnomAD database, including 2,144 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 0.15 (2144 hom., cov: 33)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.570+25399C>T		intron_variant	Intron 3 of 24	ENST00000338316.9	NP_065433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY2	ENST00000338316.9	c.570+25399C>T		intron_variant	Intron 3 of 24	1	NM_020546.3	ENSP00000342952.4
ADCY2	ENST00000498598.1	n.269+25399C>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22206 AN: 152060 Hom.: 2146 Cov.: 33

Gnomad AFR AF: 0.0446

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.146 AC: 22198 AN: 152178 Hom.: 2144 Cov.: 33 AF XY: 0.144 AC XY: 10744 AN XY: 74388

African (AFR) AF: 0.0445 AC: 1849 AN: 41550

American (AMR) AF: 0.119 AC: 1824 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5174

South Asian (SAS) AF: 0.113 AC: 546 AN: 4820

European-Finnish (FIN) AF: 0.226 AC: 2388 AN: 10558

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14322 AN: 67996

Other (OTH) AF: 0.143 AC: 303 AN: 2114

Alfa AF: 0.181 Hom.: 762

Bravo AF: 0.132

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.027
DANN	Benign	0.57
PhyloP100		-2.4
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: rs10512928; hg19: chr5-7546411;