8-37797300-C-A

Position:

• chr8-37797300-C-A

Variant summary

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

The NM_032777.10(ADGRA2):​c.32C>A​(p.Ala11Glu) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRA2 NM_032777.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.113

Genes affected

ADGRA2 (HGNC:17849): (adhesion G protein-coupled receptor A2) Predicted to enable G protein-coupled receptor activity. Involved in positive regulation of canonical Wnt signaling pathway. Part of Wnt signalosome. [provided by Alliance of Genome Resources, Apr 2022]

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=0.21496204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRA2	NM_032777.10	c.32C>A	p.Ala11Glu	missense_variant	1/19	ENST00000412232.3	NP_116166.9
ADGRA2	XM_011544481.3	c.32C>A	p.Ala11Glu	missense_variant	1/19		XP_011542783.1
ADGRA2	XM_011544482.3	c.32C>A	p.Ala11Glu	missense_variant	1/18		XP_011542784.1
ADGRA2	XM_011544483.3	c.32C>A	p.Ala11Glu	missense_variant	1/18		XP_011542785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRA2	ENST00000412232.3	c.32C>A	p.Ala11Glu	missense_variant	1/19	1	NM_032777.10	ENSP00000406367.2
ADGRA2	ENST00000315215.11	c.32C>A	p.Ala11Glu	missense_variant	1/16	1		ENSP00000323508.7
ADGRA2	ENST00000428068.5	c.140+12970C>A		intron_variant		3		ENSP00000400860.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1160020 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 560828

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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 26, 2024

The c.32C>A (p.A11E) alteration is located in exon 1 (coding exon 1) of the ADGRA2 gene. This alteration results from a C to A substitution at nucleotide position 32, causing the alanine (A) at amino acid position 11 to be replaced by a glutamic acid (E). 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	0.19
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.13	.;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.64	T;T
M_CAP	Pathogenic	0.78	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.16
Sift	Benign	0.11	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.33	B;B
Vest4		0.26
MutPred		0.27		Loss of MoRF binding (P = 0.0419);Loss of MoRF binding (P = 0.0419);
MVP		0.21
MPC		0.32
ClinPred		0.17	T
GERP RS		1.7
Varity_R		0.15
gMVP		0.35

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: chr8-37654818;