5-7746679-C-T

Position:

• chr5-7746679-C-T

Variant summary

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

The NM_020546.3(ADCY2):​c.1956+2927C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,220 control chromosomes in the GnomAD database, including 56,028 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 0.86 (56028 hom., cov: 34)
• Consequence: ADCY2 NM_020546.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY2	NM_020546.3	c.1956+2927C>T		intron_variant		ENST00000338316.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY2	ENST00000338316.9	c.1956+2927C>T		intron_variant		1	NM_020546.3	P1
	ENST00000514105.2	n.27-339G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130257 AN: 152102 Hom.: 55981 Cov.: 34

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.866

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

GnomAD4 genome AF: 0.856 AC: 130366 AN: 152220 Hom.: 56028 Cov.: 34 AF XY: 0.860 AC XY: 64002 AN XY: 74434

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.902

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.867

Alfa AF: 0.869 Hom.: 28365

Bravo AF: 0.853

Asia WGS AF: 0.903 AC: 3143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.41
DANN	Benign	0.58

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: rs6555491; hg19: chr5-7746792;