Genetic Variant ADCY2:c.1622+14_1622+15delCT (chr5-7712907-ATC-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_020546.3(ADCY2):c.1622+14_1622+15delCT 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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.708

Publications

0 publications found

Variant links:

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]

ADCY2 links:

ENSG00000250761 (HGNC:40064):

ENSG00000250761 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 782447.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1057 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020546.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY2	NM_020546.3	MANE Select	c.1622+14_1622+15delCT		intron	N/A	NP_065433.2	Q08462-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADCY2	ENST00000338316.9	TSL:1 MANE Select	c.1622+9_1622+10delTC	intron	N/A	ENSP00000342952.4	Q08462-1
ADCY2	ENST00000915366.1		c.1622+9_1622+10delTC	intron	N/A	ENSP00000585425.1
ADCY2	ENST00000915369.1		c.1622+9_1622+10delTC	intron	N/A	ENSP00000585428.1

Frequencies

GnomAD3 genomes

AF:

0.00695

AC:

1057

AN:

152168

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00658

AC:

1641

AN:

249476

AF XY:

0.00662

show subpopulations

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 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.:

AF XY:

0.00948

AC XY:

6786

AN XY:

716098

show subpopulations

African (AFR)

AF:

0.00201

AC:

AN:

32890

American (AMR)

AF:

0.00429

AC:

190

AN:

44332

Ashkenazi Jewish (ASJ)

AF:

0.00640

AC:

166

AN:

25936

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39494

South Asian (SAS)

AF:

0.00201

AC:

172

AN:

85538

European-Finnish (FIN)

AF:

0.00631

AC:

335

AN:

53116

Middle Eastern (MID)

AF:

0.000703

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.0114

AC:

12399

AN:

1089736

Other (OTH)

AF:

0.00941

AC:

560

AN:

59526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

535

1069

1604

2138

2673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

466

932

1398

1864

2330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00694

AC:

1057

AN:

152286

Hom.:

Cov.:

AF XY:

0.00637

AC XY:

474

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00236

AC:

AN:

41558

American (AMR)

AF:

0.00738

AC:

113

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00269

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00509

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0109

AC:

743

AN:

68008

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

108

161

215

269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00429

Hom.:

Bravo

AF:

0.00709

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.71

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over