rs6555465

chr5-7434504-A-Gchr5-7434504-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020546.3(ADCY2):c.408+19734A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,176 control chromosomes in the GnomAD database, including 50,963 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 0.81 (50963 hom., cov: 33)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY2	NM_020546.3	c.408+19734A>G		intron_variant		ENST00000338316.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY2	ENST00000338316.9	c.408+19734A>G		intron_variant		1	NM_020546.3	P1
ADCY2	ENST00000484965.5	n.142+19734A>G		intron_variant, non_coding_transcript_variant		3
ADCY2	ENST00000498598.1	n.107+19734A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123782 AN: 152058 Hom.: 50910 Cov.: 33

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.819

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

GnomAD4 genome AF: 0.814 AC: 123879 AN: 152176 Hom.: 50963 Cov.: 33 AF XY: 0.807 AC XY: 60053 AN XY: 74390

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.722

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.816

Alfa AF: 0.817 Hom.: 24746

Bravo AF: 0.807

Asia WGS AF: 0.634 AC: 2204 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	0.19
Dann	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs6555465; hg19: chr5-7434617;