5-7712907-ATC-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_020546.3(ADCY2):c.1622+14_1622+15del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00941 in 1,588,544 control chromosomes in the GnomAD database, including 85 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0097 (80 hom.)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.708

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 5-7712907-ATC-A is Benign according to our data. Variant chr5-7712907-ATC-A is described in ClinVar as [Benign]. Clinvar id is 782447.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 1057 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY2	NM_020546.3	c.1622+14_1622+15del		intron_variant		ENST00000338316.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY2	ENST00000338316.9	c.1622+14_1622+15del		intron_variant		1	NM_020546.3	P1
	ENST00000514105.2	n.163-4748_163-4747del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00695 AC: 1057 AN: 152168 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00237

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00739

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00658 AC: 1641 AN: 249476 Hom.: 15 AF XY: 0.00662 AC XY: 893 AN XY: 134872

Gnomad AFR exome AF: 0.00210

Gnomad AMR exome AF: 0.00368

Gnomad ASJ exome AF: 0.00579

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00175

Gnomad FIN exome AF: 0.00596

Gnomad NFE exome AF: 0.0107

Gnomad OTH exome AF: 0.00594

GnomAD4 exome AF: 0.00967 AC: 13894 AN: 1436258 Hom.: 80 AF XY: 0.00948 AC XY: 6786 AN XY: 716098

Gnomad4 AFR exome AF: 0.00201

Gnomad4 AMR exome AF: 0.00429

Gnomad4 ASJ exome AF: 0.00640

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.00201

Gnomad4 FIN exome AF: 0.00631

Gnomad4 NFE exome AF: 0.0114

Gnomad4 OTH exome AF: 0.00941

GnomAD4 genome AF: 0.00694 AC: 1057 AN: 152286 Hom.: 5 Cov.: 32 AF XY: 0.00637 AC XY: 474 AN XY: 74458

Gnomad4 AFR AF: 0.00236

Gnomad4 AMR AF: 0.00738

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00509

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.00804

Bravo AF: 0.00709

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2017

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs139089777; hg19: chr5-7713020;