Variant 17-9826074-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004246.3(GLP2R):c.11G>A(p.Gly4Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,459,278 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.000022 ( 1 hom. )

Consequence

GLP2R
NM_004246.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.560

Variant links:

Genes affected

GLP2R (HGNC:4325): (glucagon like peptide 2 receptor) This gene encodes a G protein-coupled receptor that is closely related to the glucagon receptor and binds to glucagon-like peptide-2 (GLP2). Signalling through GLP2 stimulates intestinal growth and increases villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. [provided by RefSeq, Dec 2014]

GLP2R links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03127688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLP2R	NM_004246.3 linkuse as main transcript	c.11G>A	p.Gly4Glu	missense_variant	1/13	ENST00000262441.10	NP_004237.1	O95838A0A384MTS7B2RAN4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GLP2R	ENST00000262441.10 linkuse as main transcript	c.11G>A	p.Gly4Glu	missense_variant	1/13	1	NM_004246.3	ENSP00000262441.5	O95838
GLP2R	ENST00000574745.5 linkuse as main transcript	c.-352+3789G>A		intron_variant		2		ENSP00000458242.1	I3L0P5
GLP2R	ENST00000458005.2 linkuse as main transcript	n.11G>A		non_coding_transcript_exon_variant	1/11	5		ENSP00000404471.3	H0Y6C2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000367

AC:

AN:

245306

Hom.:

AF XY:

0.0000452

AC XY:

AN XY:

132852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000300

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1459278

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

725862

show subpopulations

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:

0.000338

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.11G>A (p.G4E) alteration is located in exon 1 (coding exon 1) of the GLP2R gene. This alteration results from a G to A substitution at nucleotide position 11, causing the glycine (G) at amino acid position 4 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

0.059

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.043

DANN

Benign

0.72

DEOGEN2

Benign

0.030

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.43

M_CAP

Benign

0.0027

MetaRNN

Benign

0.031

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.14

PrimateAI

Benign

0.34

PROVEAN

Benign

0.35

REVEL

Benign

0.022

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.065

MutPred

0.27

Loss of MoRF binding (P = 0.023);

MVP

0.39

MPC

0.36

ClinPred

0.021

GERP RS

-6.6

Varity_R

0.027

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over