5-7444071-C-T

Variant names:

• chr5-7444071-C-T
• rs2017214
• NM_020546.3:c.408+29301C>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.408+29301C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 150,484 control chromosomes in the GnomAD database, including 10,465 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 0.37 (10465 hom., cov: 29)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.408+29301C>T		intron_variant	Intron 2 of 24	ENST00000338316.9	NP_065433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY2	ENST00000338316.9	c.408+29301C>T		intron_variant	Intron 2 of 24	1	NM_020546.3	ENSP00000342952.4
ADCY2	ENST00000484965.5	n.142+29301C>T		intron_variant	Intron 1 of 2	3
ADCY2	ENST00000498598.1	n.107+29301C>T		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55512 AN: 150400 Hom.: 10458 Cov.: 29

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.355

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.369 AC: 55543 AN: 150484 Hom.: 10465 Cov.: 29 AF XY: 0.371 AC XY: 27193 AN XY: 73350

African (AFR) AF: 0.343 AC: 14011 AN: 40864

American (AMR) AF: 0.427 AC: 6461 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1333 AN: 3470

East Asian (EAS) AF: 0.473 AC: 2400 AN: 5074

South Asian (SAS) AF: 0.506 AC: 2415 AN: 4772

European-Finnish (FIN) AF: 0.278 AC: 2795 AN: 10052

Middle Eastern (MID) AF: 0.360 AC: 103 AN: 286

European-Non Finnish (NFE) AF: 0.367 AC: 24916 AN: 67858

Other (OTH) AF: 0.396 AC: 826 AN: 2086

Alfa AF: 0.333 Hom.: 3321

Bravo AF: 0.375

Asia WGS AF: 0.453 AC: 1576 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.7
DANN	Benign	0.66
PhyloP100		0.58
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: rs2017214; hg19: chr5-7444184;