5-7519649-G-A

Position:

• chr5-7519649-G-A

Variant summary

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

The NM_020546.3(ADCY2):​c.409-1089G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,056 control chromosomes in the GnomAD database, including 42,402 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 0.74 (42402 hom., cov: 32)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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 (NFE) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY2	NM_020546.3	c.409-1089G>A		intron_variant		ENST00000338316.9	NP_065433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY2	ENST00000338316.9	c.409-1089G>A		intron_variant		1	NM_020546.3	ENSP00000342952	P1
ADCY2	ENST00000484965.5	n.143-1089G>A		intron_variant, non_coding_transcript_variant		3
ADCY2	ENST00000498598.1	n.108-1089G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112070 AN: 151936 Hom.: 42384 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.737 AC: 112137 AN: 152056 Hom.: 42402 Cov.: 32 AF XY: 0.738 AC XY: 54880 AN XY: 74336

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.749

Alfa AF: 0.800 Hom.: 66659

Bravo AF: 0.723

Asia WGS AF: 0.661 AC: 2300 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	1.4
DANN	Benign	0.51

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: rs6867567; hg19: chr5-7519762;