chr18-907702-G-A

Position:

• chr18-907702-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099733.2(ADCYAP1):​c.154G>A​(p.Asp52Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ADCYAP1 NM_001099733.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14

Genes affected

ADCYAP1 (HGNC:241): (adenylate cyclase activating polypeptide 1) This gene encodes a secreted proprotein that is further processed into multiple mature peptides. These peptides stimulate adenylate cyclase and increase cyclic adenosine monophosphate (cAMP) levels, resulting in the transcriptional activation of target genes. The products of this gene are key mediators of neuroendocrine stress responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22615603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCYAP1	NM_001099733.2	c.154G>A	p.Asp52Asn	missense_variant	3/5	ENST00000450565.8
ADCYAP1	NM_001117.5	c.154G>A	p.Asp52Asn	missense_variant	2/4
ADCYAP1	XM_005258081.5	c.571G>A	p.Asp191Asn	missense_variant	4/6
ADCYAP1	XM_047437288.1	c.154G>A	p.Asp52Asn	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCYAP1	ENST00000450565.8	c.154G>A	p.Asp52Asn	missense_variant	3/5	1	NM_001099733.2	P1
ADCYAP1	ENST00000579794.1	c.154G>A	p.Asp52Asn	missense_variant	2/4	1		P1
ADCYAP1	ENST00000269200.5	n.152G>A		non_coding_transcript_exon_variant	1/3	2
	ENST00000582554.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 12, 2024

The c.154G>A (p.D52N) alteration is located in exon 3 (coding exon 2) of the ADCYAP1 gene. This alteration results from a G to A substitution at nucleotide position 154, causing the aspartic acid (D) at amino acid position 52 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.64	.;T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.0	M;M
MutationTaster	Benign	0.98	D;D
PrimateAI	Uncertain	0.49	T
REVEL	Benign	0.12
Sift4G	Uncertain	0.060	T;T
Polyphen		0.13	B;B
Vest4		0.17
MutPred		0.16		Gain of relative solvent accessibility (P = 0.1684);Gain of relative solvent accessibility (P = 0.1684);
MVP		0.83
MPC		0.58
ClinPred		0.43	T
GERP RS		3.9
Varity_R		0.11
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-907703;