chr8-37784262-C-G

Position:

• chr8-37784262-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000428068.5(ADGRA2):​c.72C>G​(p.Tyr24*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00566 in 456,714 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0057 (8 hom.)
• Consequence: ADGRA2 ENST00000428068.5 stop_gained
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

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]

LOC105379381 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 8-37784262-C-G is Benign according to our data. Variant chr8-37784262-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2658537.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 837 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105379381	XR_949686.3	n.2760G>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRA2	ENST00000428068.5	c.72C>G	p.Tyr24*	stop_gained	1/6	3		ENSP00000400860.1

Frequencies

GnomAD3 genomes AF: 0.00550 AC: 837 AN: 152166 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00691

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00427 AC: 586 AN: 137212 Hom.: 3 AF XY: 0.00414 AC XY: 309 AN XY: 74592

Gnomad AFR exome AF: 0.00108

Gnomad AMR exome AF: 0.000286

Gnomad ASJ exome AF: 0.00145

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000711

Gnomad FIN exome AF: 0.0278

Gnomad NFE exome AF: 0.00619

Gnomad OTH exome AF: 0.00428

GnomAD4 exome AF: 0.00574 AC: 1748 AN: 304430 Hom.: 8 Cov.: 0 AF XY: 0.00517 AC XY: 896 AN XY: 173356

Gnomad4 AFR exome AF: 0.00104

Gnomad4 AMR exome AF: 0.000293

Gnomad4 ASJ exome AF: 0.00130

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000736

Gnomad4 FIN exome AF: 0.0282

Gnomad4 NFE exome AF: 0.00774

Gnomad4 OTH exome AF: 0.00527

GnomAD4 genome AF: 0.00550 AC: 837 AN: 152284 Hom.: 5 Cov.: 31 AF XY: 0.00638 AC XY: 475 AN XY: 74444

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.0283

Gnomad4 NFE AF: 0.00691

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00479 Hom.: 0

Bravo AF: 0.00334

TwinsUK AF: 0.00647 AC: 24

ALSPAC AF: 0.00441 AC: 17

ExAC AF: 0.00390 AC: 84

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

PLPBP: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	30
DANN	Uncertain	0.98
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.12	N
GERP RS		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs80315675; hg19: chr8-37641780; COSMIC: COSV60240286;