5-7829700-G-C

Variant names:

• chr5-7829700-G-C
• rs326175
• NM_020546.3:c.*2829G>C

Variant summary

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

The NM_020546.3(ADCY2):​c.*2829G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,272 control chromosomes in the GnomAD database, including 29,534 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 0.62 (29501 hom., cov: 32)
  • Exomes 𝑓: 0.57 (33 hom.)
• Consequence: ADCY2 NM_020546.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.*2829G>C		3_prime_UTR_variant	Exon 25 of 25	ENST00000338316.9	NP_065433.2
ADCY2	XM_011513942.3	c.*2829G>C		3_prime_UTR_variant	Exon 24 of 24		XP_011512244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY2	ENST00000338316.9	c.*2829G>C		3_prime_UTR_variant	Exon 25 of 25	1	NM_020546.3	ENSP00000342952.4

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93764 AN: 151958 Hom.: 29473 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.566 AC: 111 AN: 196 Hom.: 33 Cov.: 0 AF XY: 0.563 AC XY: 72 AN XY: 128

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.603 AC: 82 AN: 136

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 4 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.460 AC: 23 AN: 50

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.617 AC: 93852 AN: 152076 Hom.: 29501 Cov.: 32 AF XY: 0.610 AC XY: 45345 AN XY: 74340

African (AFR) AF: 0.708 AC: 29351 AN: 41478

American (AMR) AF: 0.661 AC: 10097 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2141 AN: 3470

East Asian (EAS) AF: 0.365 AC: 1888 AN: 5174

South Asian (SAS) AF: 0.469 AC: 2260 AN: 4816

European-Finnish (FIN) AF: 0.538 AC: 5682 AN: 10556

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.595 AC: 40443 AN: 67986

Other (OTH) AF: 0.634 AC: 1337 AN: 2108

Alfa AF: 0.613 Hom.: 3595

Bravo AF: 0.633

Asia WGS AF: 0.465 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.38
DANN	Benign	0.46
PhyloP100		-0.79
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: rs326175; hg19: chr5-7829813;