1-31727454-T-C

Variant names:

• chr1-31727454-T-C
• NM_001364857.2:c.4724A>G

Variant summary

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

The NM_001364857.2(ADGRB2):​c.4724A>G​(p.Glu1575Gly) 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: 32)
• Consequence: ADGRB2 NM_001364857.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65

Genes affected

ADGRB2 (HGNC:944): (adhesion G protein-coupled receptor B2) This gene encodes a a seven-span transmembrane protein that is thought to be a member of the secretin receptor family. The encoded protein is a brain-specific inhibitor of angiogenesis. The mature peptide may be further cleaved into additional products (PMID:20367554). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

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=0.08717117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRB2	NM_001364857.2	c.4724A>G	p.Glu1575Gly	missense_variant	Exon 33 of 33	ENST00000373658.8	NP_001351786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRB2	ENST00000373658.8	c.4724A>G	p.Glu1575Gly	missense_variant	Exon 33 of 33	5	NM_001364857.2	ENSP00000362762.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4724A>G (p.E1575G) alteration is located in exon 33 (coding exon 31) of the ADGRB2 gene. This alteration results from a A to G substitution at nucleotide position 4724, causing the glutamic acid (E) at amino acid position 1575 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0085	T;T;.;T;T;.;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.077	N
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.087	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.63	N;N;N;N;N;N;N
REVEL	Benign	0.027
Sift	Benign	0.13	T;T;T;T;T;T;T
Sift4G	Benign	0.73	T;T;T;T;T;T;T
Polyphen		0.83, 0.0010, 0.75	.;.;P;.;B;P;P
Vest4		0.15
MutPred		0.19		.;.;.;.;Gain of catalytic residue at E1575 (P = 0.0502);.;.;
MVP		0.043
MPC		0.91
ClinPred		0.53	D
GERP RS		2.9
Varity_R		0.086
gMVP		0.17

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: chr1-32193055;