chr5-7814229-TGAG-T

Variant names:

• chr5-7814229-TGAG-T
• rs2307998
• NM_020546.3:c.2884-2634_2884-2632delGGA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_020546.3(ADCY2):​c.2884-2634_2884-2632delGGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,146 control chromosomes in the GnomAD database, including 3,461 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (3461 hom., cov: 31)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• Publications: 3 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.2884-2634_2884-2632delGGA		intron_variant	Intron 22 of 24	ENST00000338316.9	NP_065433.2
ADCY2	XM_047416645.1	c.2884-997_2884-995delGGA		intron_variant	Intron 22 of 22		XP_047272601.1
ADCY2	XM_011513942.3	c.2746-2634_2746-2632delGGA		intron_variant	Intron 21 of 23		XP_011512244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY2	ENST00000338316.9	c.2884-2636_2884-2634delGAG		intron_variant	Intron 22 of 24	1	NM_020546.3	ENSP00000342952.4
ADCY2	ENST00000382531.7	n.595-2636_595-2634delGAG		intron_variant	Intron 5 of 5	5
ADCY2	ENST00000489501.1	n.8855-2636_8855-2634delGAG		intron_variant	Intron 2 of 4	2
ADCY2	ENST00000493243.5	n.*287-2636_*287-2634delGAG		intron_variant	Intron 5 of 6	5		ENSP00000426196.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18815 AN: 152028 Hom.: 3439 Cov.: 31

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0576

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.00556

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0970

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

GnomAD4 genome AF: 0.124 AC: 18887 AN: 152146 Hom.: 3461 Cov.: 31 AF XY: 0.118 AC XY: 8748 AN XY: 74382

African (AFR) AF: 0.402 AC: 16651 AN: 41406

American (AMR) AF: 0.0575 AC: 879 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4828

European-Finnish (FIN) AF: 0.00556 AC: 59 AN: 10620

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0147 AC: 1003 AN: 68020

Other (OTH) AF: 0.0960 AC: 203 AN: 2114

Alfa AF: 0.0812 Hom.: 261

Bravo AF: 0.140

Asia WGS AF: 0.0380 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28
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: rs2307998; hg19: chr5-7814342;