Genetic Variant ADCY5:p.Asp192_Ser193dup (chr3-123447965-C-CCCGAGT) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_183357.3(ADCY5):c.575_580dupACTCGG(p.Asp192_Ser193dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000761 in 1,313,596 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

ADCY5
NM_183357.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

Publications

0 publications found

Variant links:

Genes affected

ADCY5 (HGNC:236): (adenylate cyclase 5) This gene encodes a member of the membrane-bound adenylyl cyclase enzymes. Adenylyl cyclases mediate G protein-coupled receptor signaling through the synthesis of the second messenger cAMP. Activity of the encoded protein is stimulated by the Gs alpha subunit of G protein-coupled receptors and is inhibited by protein kinase A, calcium and Gi alpha subunits. Single nucleotide polymorphisms in this gene may be associated with low birth weight and type 2 diabetes. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ADCY5 Gene-Disease associations (from GenCC):

dyskinesia with orofacial involvement, autosomal dominant
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: G2P
neurodevelopmental disorder with hyperkinetic movements and dyskinesia
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
familial dyskinesia and facial myokymia
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
choreatic disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ADCY5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_183357.3

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY5	NM_183357.3 link	c.575_580dupACTCGG	p.Asp192_Ser193dup	conservative_inframe_insertion	Exon 1 of 21	ENST00000462833.6	NP_899200.1	O95622-1A0A384P5Q5B7Z2C7
ADCY5	NM_001378259.1 link	c.575_580dupACTCGG	p.Asp192_Ser193dup	conservative_inframe_insertion	Exon 1 of 22		NP_001365188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADCY5	ENST00000462833.6 link	c.575_580dupACTCGG	p.Asp192_Ser193dup	conservative_inframe_insertion	Exon 1 of 21	1	NM_183357.3	ENSP00000419361.1	O95622-1
ADCY5	ENST00000850916.1 link	c.737_742dupACTCGG	p.Asp246_Ser247dup	conservative_inframe_insertion	Exon 1 of 21			ENSP00000520999.1
ADCY5	ENST00000699718.1 link	c.575_580dupACTCGG	p.Asp192_Ser193dup	conservative_inframe_insertion	Exon 1 of 22			ENSP00000514543.1	A0A8V8TP58

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.61e-7

AC:

AN:

1313596

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

643072

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27716

American (AMR)

AF:

0.00

AC:

AN:

24278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20338

East Asian (EAS)

AF:

0.00

AC:

AN:

32046

South Asian (SAS)

AF:

0.00

AC:

AN:

66172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43664

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5208

European-Non Finnish (NFE)

AF:

9.61e-7

AC:

AN:

1040230

Other (OTH)

AF:

0.00

AC:

AN:

53944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Mar 05, 2018

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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3-123447965-CCCGAGT-CCCGAGTCCGAGT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over