rs2307998

Positions:

• chr5-7814229-TGAG-T
• chr5-7814229-TGAG-TGAGGAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_020546.3(ADCY2):​c.2884-2634_2884-2632del 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

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 -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/exons	MANE	UniProt
ADCY2	NM_020546.3	c.2884-2634_2884-2632del		intron_variant		ENST00000338316.9
ADCY2	XM_011513942.3	c.2746-2634_2746-2632del		intron_variant
ADCY2	XM_047416645.1	c.2884-997_2884-995del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY2	ENST00000338316.9	c.2884-2634_2884-2632del		intron_variant		1	NM_020546.3	P1
ADCY2	ENST00000493243.5	c.*287-2634_*287-2632del		intron_variant, NMD_transcript_variant		5
ADCY2	ENST00000382531.7	n.595-2634_595-2632del		intron_variant, non_coding_transcript_variant		5
ADCY2	ENST00000489501.1	n.8855-2634_8855-2632del		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.0575

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.00556

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0960

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

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: rs2307998; hg19: chr5-7814342;