chr5-7520970-G-A

Variant names:

• chr5-7520970-G-A
• rs3828628
• NM_020546.3:c.570+71G>A

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+71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,576,390 control chromosomes in the GnomAD database, including 42,149 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 0.20 (3408 hom., cov: 32)
  • Exomes 𝑓: 0.23 (38741 hom.)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.570+71G>A		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+71G>A		intron_variant	Intron 3 of 24	1	NM_020546.3	ENSP00000342952.4
ADCY2	ENST00000484965.5	n.304+71G>A		intron_variant	Intron 2 of 2	3
ADCY2	ENST00000498598.1	n.269+71G>A		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30465 AN: 151978 Hom.: 3407 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.200

GnomAD4 exome AF: 0.229 AC: 326651 AN: 1424294 Hom.: 38741 AF XY: 0.234 AC XY: 165691 AN XY: 708166

African (AFR) AF: 0.103 AC: 3394 AN: 33026

American (AMR) AF: 0.178 AC: 7880 AN: 44212

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 5459 AN: 24912

East Asian (EAS) AF: 0.338 AC: 13332 AN: 39462

South Asian (SAS) AF: 0.335 AC: 27863 AN: 83126

European-Finnish (FIN) AF: 0.279 AC: 12180 AN: 43592

Middle Eastern (MID) AF: 0.256 AC: 1431 AN: 5598

European-Non Finnish (NFE) AF: 0.221 AC: 241486 AN: 1091022

Other (OTH) AF: 0.230 AC: 13626 AN: 59344

GnomAD4 genome AF: 0.200 AC: 30471 AN: 152096 Hom.: 3408 Cov.: 32 AF XY: 0.208 AC XY: 15441 AN XY: 74336

African (AFR) AF: 0.106 AC: 4408 AN: 41510

American (AMR) AF: 0.183 AC: 2792 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3470

East Asian (EAS) AF: 0.301 AC: 1552 AN: 5148

South Asian (SAS) AF: 0.336 AC: 1617 AN: 4810

European-Finnish (FIN) AF: 0.281 AC: 2966 AN: 10570

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15712 AN: 67986

Other (OTH) AF: 0.199 AC: 421 AN: 2112

Alfa AF: 0.222 Hom.: 16669

Bravo AF: 0.186

Asia WGS AF: 0.294 AC: 1023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.34
PhyloP100		-0.049
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: rs3828628; hg19: chr5-7521083; COSMIC: COSV57873436;